Medtronic VAMC2424C100TU Instructions for Use

Download

Valiant

Thoracic Stent Graft with the Captivia® Delivery System

Instructions for Use

Trademarks may be registered and are the property of their respective owners.

Explanation of symbols that may appear on product labeling

Refer to the device labeling to see which symbols apply to this product.

Consult instructions for use at: www.medtronic.com/manuals

Catalogue number

CAUTION: Federal (USA) law restricts this device for sale by or on order of a physician.

Contents: One Device

Do not reuse

Do not use if indicator turns black

Do not use if package is damaged

Manufactured In

Manufacturer

MR Conditional

Non-pyrogenic

Peel here

Serial number

Sterilized using irradiation

Store at room temperature in a dark, dry place

Use by

FreeFlo Straight (Proximal Component)

FreeFlo Tapered (Proximal Component)

Closed Web Straight (Distal Component)

Closed Web Tapered (Distal Component)

Distal Bare Spring Straight (Distal Component)

Valiant

Thoracic Stent Graft with the Captivia® Delivery System

TABLE OF CONTENTS

1. Device Description ................................................................................................................................................................................................................... 4

2. Indications for Use ................................................................................................................................................................................................................... 5

3. Contraindications ..................................................................................................................................................................................................................... 6

4. Warnings and Precautions ....................................................................................................................................................................................................... 6

5. Adverse Events ........................................................................................................................................................................................................................ 7

6. Summary of Clinical Studies .................................................................................................................................................................................................... 8

7. Patient Selection and Treatment ............................................................................................................................................................................................ 62

8. Patient Counseling Information .............................................................................................................................................................................................. 63

9. How Supplied ......................................................................................................................................................................................................................... 63

10. Clinical Use Information ......................................................................................................................................................................................................... 63

11. Implant Instructions ................................................................................................................................................................................................................ 66

12. Troubleshooting Techniques .................................................................................................................................................................................................. 73

13. Follow-up Imaging Recommendations ................................................................................................................................................................................... 73

14. Additional Surveillance and Treatment ................................................................................................................................................................................... 74

15. Device Registration ................................................................................................................................................................................................................ 74

16. MRI Safety Information .......................................................................................................................................................................................................... 74

Instructions for Use English 3

1. Device Description

FreeFlo Straight

(Proximal Component)

FreeFlo Tapered

(Proximal Component)

Distal Bare Spring

Straight (Distal Component)

Closed Web Straight

(Distal Component)

Closed Web Tapered

(Distal Component)

The Valiant® thoracic stent graft with the Captivia® delivery system is designed for the endovascular repair of lesions of the descending thoracic aorta (DTA). When placed within the target lesion, the stent graft provides an alternative conduit for blood flow within the patient’s vasculature by excluding the lesion from blood flow and pressure.

The stent graft system is composed of 2 main components: the implantable Valiant thoracic stent graft and the disposable Captivia delivery system. The stent graft is preloaded into the delivery system, which is inserted endoluminally via the femoral or iliac artery and tracked through the patient’s vasculature to deliver the stent graft to the target site.

1.1. Stent Graft

A single, primary stent graft may be used by itself if its size is sufficient to provide the desired coverage. Alternatively, it may be used in combination with additional stent graft sections that increase the graft length either distally or proximally to the primary section.

All stent graft components are composed of a self-expanding, spring scaffold made from Nitinol wire sewn to a fabric graft with non-resorbable sutures. The metal scaffolding is composed of a series of serpentine springs stacked in a tubular configuration. Radiopaque markers are sewn onto each component of the stent graft to aid in visualization and to facilitate accurate placement. The Nitinol stents are also visible under fluoroscopy.

Stent graft components should be oversized to be larger than the measured healthy vessel. The appropriate device oversizing is incorporated into the sizing guidelines. Section 10.2 contains detailed sizing information for all stent graft components. Table 1 contains a summary of the stent graft materials.

Table 1. Stent Graft Materials

Component

Springs Nitinol wire (55% Nickel, balance Titanium with trace elements) Support Spring Nitinol wire (55% Nickel, balance Titanium with trace elements) Graft Fabric High-density woven mono-filament polyester Sutures Braided polyester Radiopaque Markers Platinum-Iridium wire

The Valiant thoracic stent graft with the Captivia delivery system does not contain natural rubber latex; however, during the manufacturing process, it may have incidental contact with latex.

1.1.1. Stent Graft Configuration Options

Material

Figure 1. Stent Graft Configuration Components

1. Proximal End

2. Distal End

3. FreeFlo

4. Closed Web

5. Bare Spring

7. Figur8 Marker

8. Zer0 Marker

9. Diameter

10. Covered Length

11. Total Length

6. Mini Support Spring

Note: This and all other product graphics appearing in this manual are not drawn to scale. They are for graphical representation only, and may appear differently under fluoroscopy. The Valiant thoracic stent graft is available in 5 configuration options: FreeFlo Straight (proximal component), FreeFlo Tapered (proximal component), Closed Web Straight (distal

component), Distal Bare Spring Straight (distal component), and Closed Web Tapered (distal component). Each consists of an 8-peak, fully covered stent and a mini support spring, which prevents the stent graft from infolding during and after deployment.

FreeFlo Straight Configuration (Proximal Component)

This configuration includes a FreeFlo proximal end and a Closed Web distal end. At the proximal end, an 8-peak bare stent extends past the covered stent graft to provide additional fixation while maintaining transvessel flow.

The FreeFlo Straight configuration stent grafts are available in diameters ranging from 22 mm to 46 mm and covered lengths of approximately 100 mm, 150 mm, and 200 mm. The proximal-end and distal-end diameters of the FreeFlo Straight configuration are constant throughout the covered length of the device.

Caution: A FreeFlo end should never be placed inside the graft covered section of another stent graft.

FreeFlo Tapered Configuration (Proximal Component)

The FreeFlo Tapered configuration has a FreeFlo proximal-end configuration and a Closed Web distal-end configuration. The proximal end of the FreeFlo Tapered configuration is 4 mm larger in diameter than its distal end. The FreeFlo Tapered configurations are available in proximal diameters ranging from 26 mm to 46 mm and distal diameters ranging from 22 mm to 42 mm. The covered length is approximately 150 mm.

Closed Web Straight Configuration (Distal Component)

This configuration includes Closed Web proximal and distal ends. The Closed Web Straight configuration stent grafts are available in diameters ranging from 22 mm to 46 mm and covered lengths of approximately 100 mm, 150 mm, and 200 mm.

The proximal and distal end diameters of the Closed Web Straight configuration are constant throughout the covered length of the device.

Caution: A Closed Web configuration should never be used as the most proximally implanted stent graft. Caution: A Closed Web Straight configuration may be implanted as the primary section only when implanting multiple stent grafts in a nontortuous segment of the descending

thoracic aorta, using the distal-to-proximal implantation technique.

4 Instructions for Use English

Distal Bare Spring Straight Configuration (Distal Component)

This configuration includes a Closed Web proximal end and a Bare Spring distal end. At the distal end, an 8-peak bare stent extends past the covered stent graft to provide additional fixation while allowing for transvessel flow.

The Distal Bare Spring Straight configuration stent grafts are available in diameters ranging from 22 mm to 46 mm and a covered length of approximately 100 mm. The proximal and distal end diameters of the Distal Bare Spring Straight configuration are constant throughout the covered length of the device.

Caution: A Bare Spring end should never be placed inside the covered section of another stent graft.

Closed Web Tapered Configuration (Distal Component)

This configuration includes Closed Web proximal and distal ends. The Closed Web Tapered configuration stent grafts are available in proximal end diameters ranging from 26 mm to 46 mm and distal end diameters ranging from 22 mm to 42 mm.

The covered length is approximately 150 mm. The proximal end of the Closed Web Tapered configuration is 4 mm larger in diameter than its distal end.

Caution: A Closed Web configuration should never be used as the most proximally implanted stent graft. Caution: A Closed Web Tapered configuration may be implanted as the primary section only when implanting multiple stent grafts in a nontortuous segment of the descending

thoracic aorta, using the distal-to-proximal implantation technique.

1.2. Delivery System

Figure 2. Captivia Stent Graft Delivery Systems

1. Luer Connector

2. Sideport Extension

3. Screw Gear

4. Slider/Handle

5. Trigger

6. Front Grip

7. Strain Relief

8. Graft Cover/Introducer Sheath

The Captivia delivery system consists of a single-use, disposable catheter with an integrated handle to provide controlled deployment. It is available in an outer diameter of 22, 24, and 25 French and a working length of approximately 83 cm. The catheter assembly is flexible and exclusively compatible with a 0.035 in (0.89 mm) guidewire. There are 2 types of Captivia delivery systems: the FreeFlo and Closed Web stent graft delivery systems. The FreeFlo system delivers the FreeFlo Straight and FreeFlo Tapered configurations. The Closed Web system delivers the Closed Web Straight, Distal Bare Spring Straight, and Closed Web Tapered configuration stent grafts. The FreeFlo system features a tip capture mechanism, which is not present in the Closed Web system.

The Captivia delivery system is a multilumen device. Each lumen serves one of the following distinct functions:

The inner member provides a lumen to allow the system to track over a 0.035 in (0.89 mm) guidewire.

•

The tip capture tube (FreeFlo stent graft delivery system only) provides a lumen to actuate the tip capture mechanism.

•

The flexible stent stop provides a lumen to aid in tracking the system through tortuous anatomy and maintains stent graft position during deployment.

•

The graft cover with stainless steel braid provides a lumen to contain the stent graft during tracking and to release the stent graft during deployment.

•

A flexible tapered tip is attached to the end of the inner member and provides a smooth transition from the guidewire to the outer graft cover. The tapered tip and graft cover are coated with a lubricious hydrophilic coating. Once activated with a sterile gauze saturated in saline, this coating will facilitate vessel access and tracking through anatomy. A distal radiopaque marker indicates the graft cover edge under fluoroscopy. A hemostasis valve at the proximal end of the delivery system minimizes blood loss and leakage during the procedure. The stent graft is deployed by rotating or retracting the integrated slider handle. When using the FreeFlo stent graft delivery system, the tip capture release handle at the rear of the delivery system is unlocked and retracted to release the bare stent.

Note: The Reliant® stent graft balloon catheter (packaged separately) can be used to assist in stent graft implantation. Note: Never use a balloon when treating a dissection.

9. Stent Stop

10. Tip Capture Mechanism

11. RO Marker Band

12. Tapered Tip

13. Back End Lock

14. Tip Capture Release Handle

15. Clamping Ring

2. Indications for Use

The Valiant thoracic stent graft with the Captivia delivery system is indicated for the endovascular repair of all lesions of the descending thoracic aorta (DTA) in patients having the appropriate anatomy including:

Iliac or femoral artery access vessel morphology that is compatible with vascular access techniques, devices, or accessories;

•

Instructions for Use English 5

nonaneurysmal aortic diameter in the range of 18 mm to 42 mm (fusiform and saccular aneurysms/penetrating ulcers), or 18 mm to 44 mm (blunt traumatic aortic injuries), or

•

20 mm to 44 mm (dissections); and nonaneurysmal aortic proximal and distal neck lengths ≥20 mm (fusiform and saccular aneurysms/penetrating ulcers), landing zone ≥20 mm proximal to the primary entry

•

tear (blunt traumatic aortic injuries, dissections). The proximal extent of the landing zone must not be dissected.

3. Contraindications

The Valiant thoracic stent graft with the Captivia delivery system is contraindicated in the following patient populations:

patients who have a condition that threatens to infect the graft

•

patients with known sensitivities or allergies to the device materials (Table 1)

•

Also consider the information in Patient Selection (Section 4.2).

4. Warnings and Precautions

Caution: Read all instructions carefully. Failure to properly follow the instructions, warnings, and precautions may lead to serious consequences or injury to the patient.

4.1. General

The Valiant thoracic stent graft with the Captivia delivery system should only be used by physicians and medical personnel trained in vascular interventional techniques,

•

including training in the use of this device. Specific training expectations are described in Physician Training Requirements (Section 10.1). Always have a vascular surgery team available during implantation or reintervention procedures in the event that conversion to open surgical repair is necessary.

•

Caution: Federal (USA) law restricts this device for sale by or on the order of a physician.

•

If preoperative case planning measurements are not certain, an inventory of device lengths and diameters necessary to complete the procedure should be available to the

•

physician.

■

Use of the device outside the recommended anatomical sizing may result in serious device related events.

4.2. Patient Selection

The Valiant thoracic stent graft with the Captivia delivery system is not recommended in patients who cannot undergo, or who will not be compliant with, the necessary

•

preoperative and postoperative imaging and implantation procedures described in Section 10 through Section 13. The Valiant thoracic stent graft with the Captivia delivery system is not recommended in patients who cannot tolerate contrast agents necessary for intraoperative and

•

postoperative follow-up imaging. The use of this device requires administration of radiographic agents. Patients with pre-existing renal insufficiency may have an increased risk of postoperative renal failure.

•

The Valiant thoracic stent graft with the Captivia delivery system is not recommended in patients exceeding weight or size limits necessary to meet imaging requirements.

•

Inappropriate patient selection may result in poor performance.

•

Prior to the procedure, preoperative planning for access and placement should be performed. See Recommended Device Sizing (Section 10.2). Key anatomic elements that

•

may affect successful exclusion of the lesion include tortuosity, short landing zone(s) [<20 mm], and thrombus or calcium formation at the implantation sites. In the presence of anatomical limitations, a longer landing zone and additional stent grafts may be required to obtain adequate sealing and fixation.

The Valiant thoracic stent graft with the Captivia delivery system is intended for use in aortic neck diameters in the range of 18 to 42 mm (TAA), or landing zones in the range

•

of 18 to 44 mm (BTAI) or 20 to 44 mm (dissection) and in aortic proximal and distal neck lengths of ≥20 mm (TAA) or landing zones ≥20 mm proximal to the primary entry tear (BTAI, dissection). The most proximal extent of the landing zone must not be dissected. Coverage of the LSA may be necessary to gain the needed landing zone.

■

Ensure that the Valiant thoracic stent graft is placed in a landing zone without evidence of circumferential thrombus, intramural hematoma, dissection, ulceration, or aneurysmal involvement. Failure to do so may result in inadequate exclusion or vessel damage, including perforation. Landing the proximal end of the device in dissected tissue could increase the risk of damage to the septum and could lead to new septal tears, aortic rupture, retrograde dissection, or other complications.

Coverage of the left subclavian artery without revascularization may increase the risk of stroke.

•

The safety and effectiveness of the Valiant thoracic stent graft with the Captivia delivery system has not been evaluated in the following patient situations or populations:

•

■

The patient requires planned placement of the covered proximal end of the stent graft requires implant to occur in Zone 0 or Zone 1 (Figure 3).

■

The patient’s access vessel, as determined by treating physician, precludes safe insertion of the delivery system. Note: Iliac conduits may be used to ensure the safe insertion of the delivery system.

■

The patient has a significant or circumferential aortic mural thrombus, which could compromise fixation and seal of the implanted stent graft.

■

The patient has a TAA with a contained rupture.

■

The patient has acute, uncomplicated Type B dissection.

■

The patient has chronic Type B dissection.

■

The patient has received a previous stent or stent graft or previous surgical repair in the descending thoracic aortic area.

■

The patient has pseudoaneurysms resulting from previous graft placement.

■

The patient will be undergoing a concomitant surgical or endovascular treatment of an infrarenal aortic aneurysm.

■

The patient has connective tissue disease (for example, Marfan syndrome or medial degeneration).

■

The patient has a history of bleeding diathesis or coagulopathy, or refuses blood transfusions.

■

The patient has had a cerebrovascular accident (CVA) within 3 months of the procedure.

■

The patient has a known hypersensitivity or contraindication to anticoagulants or contrast media, which is not amenable to pretreatment.

■

The patient has active systemic infections.

■

The patient has an aortic fistula.

■

The patient has aortitis or an inflammatory aneurysm.

■

The patient has a mycotic aneurysm.

■

The patient is a pregnant female.

6 Instructions for Use English

Figure 3. Covered Stent Graft Placement Zones

■

The patient is less than 18 years old.

The long-term safety and effectiveness of the Valiant thoracic stent graft with the Captivia delivery system has not been established. All patients should be advised that

•

endovascular treatment requires lifelong, regular follow-up to assess the integrity and performance of the implanted endovascular stent graft. Patients with specific clinical findings (for example, enlarging aneurysm [>5 mm], endoleak, migration, inadequate seal zone, or continued flow into the false lumen in the case of a dissection) should receive enhanced follow-up. Specific follow-up guidelines are described in Follow-up Imaging Recommendations (Section 13).

Strict adherence to the Valiant thoracic stent graft with the Captivia delivery system sizing guidelines (Table 3 to Table 9) is expected when selecting the device size. The

•

appropriate device oversizing is incorporated into the sizing guidelines. Sizing outside of this range can potentially result in endoleak, fracture, migration, infolding, or graft wear.

Intervention or conversion to standard open surgical repair following initial endovascular repair should be considered for patients experiencing enlarging aorta and/or

•

endoleak. An increase in aneurysm size, false lumen size, or persistent endoleak may lead to rupture.

4.3. Implant Procedure

Wrinkling of stent graft material may promote thrombus formation. If this occurs, inflate a conformable balloon within the deployed stent graft lumen to reduce wrinkling of the

•

material. Note: Medtronic recommends the Reliant stent graft balloon catheter for use with the Valiant thoracic stent graft. Data is not available for remodeling the Valiant thoracic stent

graft with other balloon catheters. Caution: Never use a balloon when treating a dissection.

■

Use the Reliant stent graft balloon catheter according to the Instructions for Use (IFU) supplied with the product. Do not attempt to use the Reliant stent graft balloon catheter before completely reading and understanding the IFU supplied with the product.

■

Do not over-inflate the balloon.

■

Care should be taken not to balloon outside of the Valiant thoracic stent graft. If the proximal and distal radiopaque markers of the Reliant stent graft balloon catheter are not completely within the covered portion of the Valiant thoracic stent graft, there is an increased risk of vessel injury, rupture, or possible patient death.

■

Care should be taken when inflating the balloon, especially with calcified, tortuous, stenotic, or otherwise diseased vessels. Inflate slowly. It is recommended that a backup balloon be available.

A seal zone <20 mm could increase the risk of endoleak or migration of the stent graft. Migration may also be caused by deployment of the proximal stent into a thrombus-

•

filled or severely angled vessel wall. Manipulation of wires, balloons, catheters, or endografts in the thoracic aorta may lead to vascular trauma, including aortic dissection and embolization.

•

Do not bend, kink, or otherwise alter the Captivia delivery system prior to implantation because it may cause deployment difficulties.

•

Discontinue advancement of the guidewire or delivery system if resistance is felt. The cause of resistance must be assessed in order to avoid vessel or delivery catheter

•

damage. Wire fractures are more likely to occur in conditions with an excessively oversized endoprosthesis, flexion, kinking, or bending during cardiac or respiratory cycles. Wire

•

fractures may have clinical consequences, such as endoleak, endoprosthesis migration, or adjacent tissue damage. Oversize the aortic portion of the stent graft by 10 to 20%, as appropriate for the patient. For additional sizing information, see Recommended Device Sizing (Section 10.2).

•

Caution: Oversizing of the stent graft to the vessel >10% may be unsafe in the presence of dissecting tissue or intramural hematoma. Due to the increased risk of dislodging material during distal repositioning of the Valiant thoracic stent graft, it is not recommended to position the device higher in the aorta in

•

the presence of excessive calcification or thrombus formation. See Positioning the Captivia Delivery System (Section 11.6). Do not advance the Valiant thoracic stent graft with the Captivia delivery system when it is partially deployed and is apposed to the vessel wall.

•

The proximal end of the covered Valiant thoracic stent graft should not be placed beyond the origin of the left common carotid artery (ie, Zone 0 or Zone 1) (Figure 3). FreeFlo

•

and Bare Spring Straight ends should never be placed inside the fabric covered section of another stent graft. This may result in abrasion of the fabric by the bare spring and result in graft material holes or broken sutures.

Ensure that the Valiant devices are placed in a landing zone without evidence of circumferential thrombus, intramural hematoma, dissection, ulceration, or aneurysmal

•

involvement. Failure to do so may result in inadequate exclusion or vessel damage, including perforation. Landing the proximal end of the device in dissected tissue could increase the risk of damage to the septum and could lead to new septal tears, aortic rupture, retrograde dissection, or other complications.

When treating acute dissections with multiple devices, it is recommended to deploy the proximal device first. Inadvertent pressurization of the false lumen may result in

•

retrograde dissection. When treating dissections, ensure the distal end of the device is in a straight portion of the aorta in order to reduce risk of septum damage.

•

Consider adjunctive procedures to restore blood flow to malperfused branch vessels. Additional procedures during treatment in the Medtronic Dissection Trial included, but

•

were not limited to, peripheral stenting and surgical bypass (e.g., carotid subclavian, fem-fem). Endoleak left untreated during the implantation procedure must be carefully monitored after the implantation procedure.

•

Avoid occluding arterial branches that do not have collateral or protected perfusion to end organs or body structures. If the left subclavian artery (LSA) is to be covered, check

•

the blood flow of the vertebral or cerebral arteries and the retrograde flow of the LSA. If occlusion of the left subclavian artery ostium is required to obtain adequate neck length/landing zone for fixation and sealing, transposition, or bypass of the LSA should be considered.

Caution: Patients with a patent LIMA (left internal mammary artery)-LAD (left anterior descending artery) bypass should not be considered for coverage of the LSA unless additional bypasses are performed prior to the stent graft procedure.

4.4. MRI Safety Information

Nonclinical testing has demonstrated that the Valiant thoracic stent graft is MR Conditional. It can be scanned safely in 1.5 T and 3.0 T MR systems only, with using only the specific testing parameters (Section 13.5). Additional MRI safety information is found in Section 13.5.

5. Adverse Events

5.1. Potential Adverse Events

Adverse events or complications associated with the use of the Valiant thoracic stent graft with the Captivia delivery system that may occur or require intervention include, but are not limited to:

Instructions for Use English 7

• Access failure

• Access site complications (eg, spasm, trauma, bleeding, rupture, dissection)

• Adynamic Ileus

• Allergic reaction (to contrast, antiplatelet therapy, stent graft material)

• Amputation

• Anesthetic complications

• Aortic expansion (e.g. aneurysm, false lumen)

• Aneurysm rupture

• Angina

• Aortic vessel rupture

• Arrhythmia

• Arterial stenosis

• Atelectasis

• Blindness

• Bowel ischemia/infarction

• Bowel necrosis

• Bowel obstruction

• Branch vessel occlusion

• Buttock claudication

• Cardiac tamponade

• Catheter breakage

• Cerebrovascular accident (CVA)/Stroke

• Change in mental status

• Coagulopathy

• Congestive heart failure

• Contrast toxicity

• Conversion to surgical repair

• Death

• Deployment difficulties/ failures

• Dissection, perforation, or rupture of the aortic vessel & surrounding vasculature

• Embolism

• Endoleaks

• Excessive or inappropriate radiation exposure

• Extrusion/erosion

• Failure to deliver the stent graft

• Femoral neuropathy

• Fistula (aortobronchia, aortoenteric, aortoesophogeal, arteriovenous, lymph)

• Gastrointestinal bleeding/complications

• Genitourinary complications

• Hematoma

• Hemorrhage/bleeding

• Hypotension/hypertension

• Infection or fever

• Insertion or removal difficulty

• Intercostal pain

• Intramural hematoma

• Leg edema/foot edema

• Lymphocele

• Myocardial infarction

• Neuropathy

• Occlusion – Venous or Arterial

• Pain/Reaction at catheter insertion site

• Paralysis

• Paraparesis

• Paraplegia

• Paresthesia

• Perfusion of the false lumen

• Peripheral ischemia

• Peripheral nerve injury

• Pneumonia

• Post-implant syndrome

• Post-procedural bleeding

• Procedural bleeding

• Prosthesis dilatation

• Prosthesis infection

• Prosthesis rupture

• Prosthesis thrombosis

• Pseudoaneurysm

• Pulmonary edema

• Pulmonary embolism

• Reaction to anaesthesia

• Renal failure

• Renal insufficiency

• Reoperation

• Respiratory depression or failure

• Retrograde Type A dissection

• Sepsis

• Seroma

• Shock

• Spinal neurological deficit

• Stent graft material failure (including breakage of metal portion of device)

• Stent graft migration

• Stent graft misplacement

• Stent graft occlusion

• Stent graft twisting or kinking

• Transient ischemic attack (TIA)

• Thrombosis

• Tissue necrosis

• Vascular ischemia

• Vascular trauma

• Wound dehiscence

• Wound healing complications

• Wound infection

5.2. Adverse Event Reporting

Any adverse event or clinical incident involving the Valiant thoracic stent graft with the Captivia delivery system should be immediately reported to Medtronic Vascular. To report an incident in the US, call (800) 465-5533.

6. Summary of Clinical Studies

The clinical evidence supporting the safety and effectiveness of the Valiant thoracic stent graft with the Captivia delivery system is from a combination of 5 clinical studies:

Study

Medtronic Dissection Trial to evaluate the Valiant thoracic stent graft with the Captivia delivery system in the treatment of acute, complicated Type B dissection RESCUE US Clinical Study to evaluate the Valiant thoracic stent graft with the Captivia delivery system in the treatment of severe blunt thoracic aortic injuries/transection

Valiant Thoracic Stent Graft Clinical Study (VALOR II)

Valiant Captivia OUS Registry to provide confirmatory clinical information to support the engineering evaluation of the modified Captivia delivery system

Talent® Captivia Study

Subsequent to the enrollment in VALOR II, the delivery system was updated from the Xcelerant to the Captivia delivery system. The Captivia delivery system is a design iteration of the Xcelerant delivery system. The primary difference between the 2 delivery systems is the incorporation of a tip capture mechanism designed to constrain the proximal bare springs of the FreeFlo stent graft until proper positioning has been obtained.

6.1. Medtronic Dissection Trial

The Medtronic Dissection Trial was a prospective, non-randomized, multicenter, single-arm study. The primary objective was to evaluate the safety and effectiveness of the Valiant thoracic stent graft in the treatment of acute, complicated Type B dissection, as determined by all-cause mortality within 30 days of the index procedure, compared to a performance goal based on TEVAR and open surgical repair outcomes. A sample size of 50 subjects was planned to provide 80% power to establish a mortality rate lower than the performance goal using a one-sided exact test at the 0.05 statistical significance level. An adaptive design was utilized such that additional subject enrollment (up to 84 subjects total) would be allowed as necessary to meet the performance goal. However, the performance goal was met after evaluation of the primary endpoint for the initial 50 subjects.

Secondary observations included adverse events, technical success, secondary procedures, aortic remodeling, false lumen perfusion, and all-cause mortality within 12 months. A total of 89 subjects were screened for enrollment in the study. The reasons for exclusion were lack of malperfusion or rupture (n=10), presence of chronic dissection >14 days

(n=7), inability to consent (n=3), no indication for intervention (n=3), inclusion criteria not met (n=2), fenestrated (n=2), intramural hematoma without dissection (n=2), <20 mm proximal landing zone (n=2), unreliable for follow-up (n=1), patient refused (n=1), previous repair (n=1), medically managed (n=1), history of aortic repair (n=1), unstable for surgery (n=1), Marfan's Syndrome (n=1), and retrograde extension to LCC (n=1).

Data was collected at the pre-treatment evaluation, during the procedure, post-operatively and at hospital discharge. After discharge, subjects were evaluated at one, six, and 12 months and are evaluated annually thereafter for five years post-implant.

A Clinical Events Committee met to review and adjudicate all deaths and unanticipated adverse device effects (UADEs) for relatedness to the aorta, device and procedure. No UADEs were identified in the study. A Data Monitoring Committee (DMC) met to review safety data and monitor the overall conduct of the study. The DMC reviewed the 30-day data for the first 20 subjects and for the first 30 subjects. The committee recommended that the trial continue without modifications. A central imaging core lab was utilized to provide independent evaluation of imaging findings. Both site and core lab data are included in this report, as appropriate. The data cut off for this report was May 30, 2013.

6.1.1. Suitability of the Performance Goal

The expected 30-day mortality rate was 11%. The Performance Goal was set at 25% after considering the mortality rates from 1) the Society for Vascular Surgery (SVS) Master Access File (MAF) of 85 acute, complicated dissection subjects; 2) the literature on open surgical repair and 3) the literature on TEVAR treated dissection patients. The performance goal allowed for reasonable variances due to the low rate of occurrence, the low baseline sample size in the literature and MAF and for variances in outcomes due to both a potential difference in patient complicating factors and a broader selection of physicians implanting the device in this study.

Objective

(BTAI) in the descending thoracic aorta to demonstrate the safe and effective use of the Valiant thoracic stent graft for the treatment of fusiform aneurysms and saccular aneur-

ysms/penetrating ulcers of the descending thoracic aorta in subjects who were candidates for endovascular repair

to provide confirmatory clinical information to support the engineering evaluation of the modified Captivia delivery system

8 Instructions for Use English

6.1.2. Subject Accountability and Follow-up

Subject Follow -up

% (m/n)

Subject Imaging

% (m/n)

Subj ects with Adequate Imaging to Assess the Parameter

% (m/n)

Subject Events Occurring Before Next Visit

Implant

and

Follow-up

Eligible

Clinical

Follow -

Imaging

Follow -

CT/MR

Imaging

Chest

X- Ray

Additional

Imaging

Modalities

Max

DTA

Diameter

Change in

Max DTA

Diameter

from

Discharge

Endoleak

Migration

Integrity

Enrolled

but not

Implanted

Withdrawal

Conversion

to Surgery Death

Lost to

Follow -

Not

Due

for

Visit

Implant

Events

Between

Implant

and

Discharge

0 3

Discharge

97.9%

(46/47)

80.9%

(38/47)

76.6% (36/47)

2.1% (1/47)

76.6%

(36/47)

68.1%

(32/47)

78.7%

(37/47)

Events

Between

Discharge

and

1-Month

0 1

1-Month

97.8%

(45/46)

97.8%

(45/46)

97.8%

(45/46)

91.3%

(42/46)

0.0% (0/46)

95.7%

(44/46)

87.0%

(40/46)

97.8%

(45/46)

95.7%

(44/46)

Events

Between

1-Month

and

6-Month

0 3

6-Month

87.8%

(36/41)

82.9%

(34/41)

80.5%

(33/41)

68.3%

(28/41)

0.0% (0/41)

80.5%

(33/41)

80.5%

(33/41)

78.0%

(32/41)

78.0%

(32/41)

78.0%

(32/41)

Events

Between

6-Month

and

12-Month

0 1

12-Month

90.0%

(36/40)

85.0%

(34/40)

85.0%

(34/40)

75.0%

(30/40)

0.0% (0/40)

85.0%

(34/40)

85.0%

(34/40)

85.0%

(34/40)

85.0%

(34/40)

85.0%

(34/40)

0 8

1 0

Total Deaths

Deaths Post Conversion to Surgery

Total

conversion to surgery (CTS) plus death (D) plus lost to follow up (LTF) plus not due for next visit (NDNV) subjects. ET = EPI – (ENI + W + CTS + D + LTF + NDNV)

Percentages for eligible subjects are based on number of all subjects enrolled by snapshot date and for clinical and site reported imaging follow-up are based on number of subjects who had follow-up visit within window divided

by number of eligible subjects. Within window visits are defined as: for discharge: day 0 to the day of discharge, for 1 month: 16-44 days, for 6 months: 123-243 days, for 12 months: 275-455 days.

The first post-implant image will be used as the baseline image for measuring the change in DTA diameter and migration.

36 subjects had CTs and 2 subjects had X-ray imaging only. X-ray imaging was not required at pre-discharge and thus these two patients do not show up under the X-ray column.

m = number of subjects in category, n = number of subjects with available values

Fifty subjects (50) were enrolled in this study between June 2010 and May 2012, at 16 investigational sites. All enrolled subjects underwent endovascular repair with the Valiant thoracic stent graft. Figure 4 summarizes the subject accountability and compliance by study interval.

Figure 4. Subject Follow up, Imaging and Accountability

6.1.3. Subject Population Demographics and Baseline Parameters

Figure 5 through Figure 8 provide baseline parameters of the study subjects including demographics, medical history, clinical symptoms, and initial dissection assessment via imaging at presentation.

Instructions for Use English 9

Subject Demographic

Age (years)

Mean ± SD

Median

Min, Max

Sex % (m/n)

Male

Female

Hispanic or Latino

Not Hispanic or Latino

Not Available

Refuses to answer

Race % (m/n)

Caucasian

African American

Asian

Native Hawaiian or Other Pacific Islander

American Indian or Alaskan Native

Other

Not Available

Medtronic Dissection Trial

Subjects1

57.2 ± 12.9

56.5

18, 83

80.0% (40/50)

20.0% (10/50)

10.0% (5/50)

88.0% (44/50)

2.0% (1/50)

0.0% (0/50)

62.0% (31/50)

22.0% (11/50)

12.0% (6/50)

0.0% (0/50)

4.0% (2/50)

0.0% (0/50)

SVS MAF

Subjects

58.3 ± 15.4

59.0

25, 88

72.9% (62/85)

27.1% (23/85)

14.3% (12/84)

85.7% (72/84)

0.0% (0/84)

52.9% (45/85)

27.1% (23/85)

3.5% (3/85)

1.2% (1/85)

0.0% (0/85)

14.1% (12/85)

Ethnicity % (m/n)

Based on number of ITT subjects with available data. ITT subjects are all enrolled subjects.

m = number of subjects in category, n = number of subjects with available values

Figure 5. Subject Demographics

Figure 6 summarizes the medical history of the subjects with available data. Among the subjects in the Medtronic Dissection Trial, conditions that are common to cardiovascular disease were represented, specifically hypertension (90.0%), current tobacco use (43.8%), hyperlipidemia (32.7%), peripheral vascular disease(14.0%), coronary artery disease (12.0%), abdominal aortic aneurysm (12.0%) and ascending thoracic aneurysm (8.0%). Similarly, the SVS MAF subjects had a high incidence of hypertension (83.5%) and current tobacco use (32.5%). Information on other categories was unavailable.

Among the SVS MAF subjects, 11.8% had vascular disorders as compared to 44% in the Medtronic Dissection Trial group and 7.1% had GU/Renal disorders as compared to 38% in the Dissection Trial group.

10 Instructions for Use English

Congestive Heart Failure

Hypertension

Arrhythmia

Angina

Coronary Artery Disease

Coronary Artery Bypass Grafting (CABG)

Percutaneous Coronary Intervention

Other Cardiac

Vascular

Abdominal Aortic Aneurysm

Ascending Thoracic Aneurysm

Family History of Aneurysms

Peripheral Vascular Disease

Carotid Artery Disease

Lower Extremity Claudication

Lower Extremity Rest Pain

Lower Extremity Ulcers

DVT

Pulmonary Embolus

Other Vascular

Pulmonary

COPD

Mechanical Ventilation (for > 24 hrs)

Other Chronic Pulmonary Disease

Cerebrovascular/Neurological

Transient Ischemic Attack (TIA)

Stroke/Cerebrovascular Accident (CVA)

Paraplegia

Paraparesis

Other Cerebrovascular/Neurological

GU/Renal

Hemodialysis

Chronic Renal Failure

Renal Insufficiency

Other GU/Renal

Connective Tissue Disease

Marfan Syndrome

Ehlers Danlos

Other Connective Tissue Disease

Diabetes Mellitus

Insulin Dependent

Cancer

Liver Disease

GI Conditions

Bleeding Disorder

Hyperlipidemia

Other Systemic Conditions

History of Alcohol Abuse

Tobacco Use

Current Smoker

Former Smoker

Never Smoked

Other Medical History

Based on number of ITT subjects with available data Not all subjects answered every medical history question and that is reflected in the denominator for each category. In cases where the data was missing, the sites were queried and the data was unavailable. m = number of subjects in category, n = number of subjects with available values. A subject may have more than one condition; hence, number of subjects at higher level may not be equal to the total at lower level.

Fisher's exact test

Subject Medical History

SVS MAF

Subjects

% (m/n)

89.4% (76/85)

10.6% (9/85)

83.5% (71/85)

11.8% (10/85)

12.9% (11/85)

10.6% (9/85)

2.4% (2/85)

7.1% (6/85)

0.0% (0/85)

3.5% (3/85)

2.4% (2/85)

1.2% (1/85)

0.0% (0/85)

7.1% (6/85)

4.7% (4/85)

12.9% (11/85)

0.0% (0/85)

32.5% (27/83)

37.3% (31/83)

30.1% (25/83)

Medtronic Dissection Trial

Subjects % (m/n)1

90.0% (45/50)

8.0% (4/50)

90.0% (45/50)

6.0% (3/50)

8.0% (4/50)

14.0% (7/50)

12.0% (6/50)

2.0% (1/50)

4.0% (2/50)

44.0% (22/50)

12.0% (6/50)

8.0% (4/50)

4.3% (2/47)

14.0% (7/50)

4.1% (2/49)

6.1% (3/49)

6.0% (3/50)

4.0% (2/50)

6.0% (3/50)

0.0% (0/50)

14.0% (7/50)

18.0% (9/50)

4.0% (2/50)

6.0% (3/50)

12.0% (6/50)

8.0% (4/50)

0.0% (0/50)

2.0% (1/50)

38.0% (19/50)

2.0% (1/50)

0.0% (0/50)

16.0% (8/50)

0.0% (0/50)

8.0% (4/50)

2.0% (1/50)

14.0% (7/50)

0.0% (0/50)

22.4% (11/49)

32.7% (16/49)

4.1% (2/49)

4.0% (2/50)

43.8% (21/48)

35.4% (17/48)

20.8% (10/48)

40.0% (20/50)

4.0% (2/50)

24.0% (12/50)

Cardiac

0.0% (0/50)

0.0% (0/49)

9.4% (8/85)

p-value

>0.999

0.767

0.443

0.371

0.571

<0.001

0.458

0.212

0.051

>0.999

0.530

>0.999

0.370

<0.001

0.296

0.572

0.412

>0.999

0.355

Figure 6. Subject Medical History

Instructions for Use English 11

Clinical symptoms reported at onset/presentation are summarized in Figure 7. The most common symptoms for the Medtronic Dissection Trial subjects were back/chest pain (88.0%), hypertension (52.0%), abdominal pain (36.0%), nausea/vomiting (24.0%) and paraparesis (12.0%). The most common symptoms for the SVS MAF subjects at onset were pain (76.5%), hypertension (43.5%) and bleeding (8.2%).

Of the 50 subjects enrolled in the study, 40 (80%) experienced malperfusion with no rupture, 7 (14%) experienced rupture with no malperfusion and 3 (6%) experienced both malperfusion and rupture.

12 Instructions for Use English

Rupture % (m/n)

Malperfusion % (m/n)

Visceral Ischemia % (m/n)

Renal Ischemia % (m/n)

Lower Limb Ischemia % (m/n)

Spinal Cord Ischemia % (m/n)

At Onset

Duration from Onset to Presentation (days)

Median

Min, Max

Duration from Onset to Procedure (days)

Mean ± SD

Median

Min, Max

Hypertension % (m/n)

Pain % (m/n)

Abdominal Pain % (m/n)

Back/Chest Pain % (m/n)

Bleeding % (m/n)

Paraplegia % (m/n)

Paraparesis % (m/n)

Headache % (m/n)

Syncope/Altered Consciousness % (m/n)

Nausea/Vomiting % (m/n)

At Presentation

Duration from Presentation to Procedure (days)

Mean ± SD

Median

Min, Max

Hypertension % (m/n)

Pain % (m/n)

Abdominal Pain % (m/n)

Back/Chest Pain % (m/n)

Bleeding % (m/n)

Paraplegia % (m/n)

Paraparesis % (m/n)

Headache % (m/n)

Syncope/Altered Consciousness % (m/n)

Nausea/Vomiting % (m/n)

New Medications After Admission

Inotropic Support % (m/n)

Anti-Hypertensives % (m/n)

Based on number of ITT subjects with available data m = number of subjects in category, n = number of subjects with available values

A t-test was performed on duration measures; Fisher's exact test was carried out on other parameters.

Medtronic Dissection Trial

Subjects1

20.0% (10/50)

86.0% (43/50)

40.0% (20/50)

42.0% (21/50)

40.0% (20/50)

6.0% (3/50)

2.0% (1/50)

1.4 ± 2.4

0.0

0, 10

4.7 ± 4.5

3.0

0, 23

52.0% (26/50)

94.0% (47/50)

36.0% (18/50)

88.0% (44/50)

2.0% (1/50)

4.0% (2/50)

12.0% (6/50)

4.0% (2/50)

0.0% (0/50)

24.0% (12/50)

3.3 ± 3.6

1.5

0, 14

60.0% (30/50)

92.0% (46/50)

42.0% (21/50)

78.0% (39/50)

2.0% (1/50)

4.0% (2/50)

14.0% (7/50)

4.0% (2/50)

2.0% (1/50)

18.0% (9/50)

16.0% (8/50)

84.0% (42/50)

SVS MAF

Subjects

31.8% (27/85)

71.8% (61/85)

14.1% (12/85)

25.9% (22/85)

40.0% (34/85)

2.4% (2/85)

5.9% (5/85)

2.9 ± 3.4

1.0

0, 14

43.5% (37/85)

76.5% (65/85)

8.2% (7/85)

Ischemia (Other) % (m/n)

Mean ± SD

p-value

>0.999

0.165

0.089

0.001

0.058

0.359

0.412

0.015

0.375

0.009

0.257

Figure 7. Clinical Symptoms

Instructions for Use English 13

Based on number of ITT subjects with available data

m = number of subjects in category n = number of subjects with available data

28.6% (14/49)

90.0% (45/50)

6.0% (3/50)

4.0% (2/50)

48.0% (24/50)

10.0% (5/50)

14.0% (7/50)

8.0% (4/50)

14.0% (7/50)

6.0% (3/50)

74.0% (37/50)

22.0% (11/50)

4.0% (2/50)

6.1% (3/49)

2.0% (1/49)

0.0% (0/49)

20.4% (10/49)

6.1% (3/49)

4.1% (2/49)

20.4% (10/49)

12.2% (6/49)

% (m/n)

Initial Dissection Assessment

Site of Proximal Entry Tear

Proximal Descending Aorta

Mid Descending Aorta

Distal Descending Aorta

Visible Re-entry Tears

None

One Tear

Two Tears

Three Tears

Four Tears

Five Tears

Most Proximal Aspect of Dissection

At LSA

Greater Than 2 cm Distal to LSA

Mid Descending Aorta

Most Distal Aspect of Dissection

Thoracic Aorta

Celiac Trunk

Superior Mesenteric Artery

Abdominal Aorta (Suprarenal)

Abdominal Aorta (Infrarenal)

Aortic Bifurcation

Common Iliac

Internal Iliac

External Iliac

Femoral Artery

ASA Physical Classification

Based on number of ITT subjects with available data

m = number of subjects in category, n = number of subjects with available values

III

Not assessed

SVS MAF

Subjects

% (m/n)

22.4% (19/85)

0.0% (0/85)

2.4% (2/85)

64.7% (55/85)

10.6% (9/85)

Dissection

Subjects % (m/n)

0.0% (0/50)

6.0% (3/50)

22.0% (11/50)

66.0% (33/50)

6.0% (3/50)

0.0% (0/85) 0.0% (0/50)

14 Instructions for Use English

Figure 8. Initial Dissection Assessment

Figure 9. ASA Physical Classification

Thoracic Aortic Measurements: Diameters (mm)

AD1: Maximum Thoracic Aortic Centerline Diameter

Mean ± SD

Median

Min, Max

AD2: Maximum True Lumen Diameter at AD1

Mean ± SD

Median

Min, Max

AD3: Maximum False Lumen Diameter at AD1

Mean ± SD

Median

Min, Max

D1: Diameter of Distal Margin of LCCA (Long Axis of Ellipse)

Mean ± SD

Median

Min, Max

Diameter at Proximal Landing Zone if Different from D1

Mean ± SD

Median

Min, Max

Right External Iliac Artery Diameter

Mean ± SD

Median

Min, Max

Left External Iliac Artery Diameter

Mean ± SD

Median

Min, Max

Site

Reported

40.6 ± 7.5

40.0

18, 60

19.9 ± 9.9

20.0

3, 52

23.0 ± 8.9

23.5

0, 40

32.0 ± 4.3

32.0

20, 44

31.4 ± 3.1

31.0

22, 38

10.2 ± 2.6

10.0

5, 18

10.0 ± 3.0

10.0

0, 18

Based on number of ITT subjects with available data

Figure 10. Aortic and Iliac Measurements at Presentation: Diameters

Instructions for Use English 15

Thoracic Aortic Measurements: Lengths (mm)

L1: Landing Zone (Distal Margin of LCCA to Primary Entry Tear)

Mean ± SD

Median

Min, Max

L2: Total Length of Aortic Dissection (Thoracic and Abdominal)

Mean ± SD

Median

Min, Max

L3: Total Thoracic Aortic Length (LCCA to Celiac)

Mean ± SD

Median

Min, Max

Site

Reported

39.7 ± 34.0

29.5

20, 223

376.4 ± 111.4

378.0

50, 580

278.4 ± 63.6

271.0

190, 580

Based on number of ITT subjects with available data

Figure 11. Aortic Measurements at Presentation: Lengths

Number of Devices Implanted

Subjects % (m/n)

62.0% (31/50)

32.0% (16/50)

6.0% (3/50)

Based on number of implanted subjects with available data

m = number of subjects in category, n = number of subjects with available values

Device Diameter (mm)

Number of Devices Implanted (n)

22 0

24 0

26 1

28 0

30 1

32 13

34 13

36 7

38 10

40 4

42 1

44 0

46 0

Based on number of implanted subjects with available data

6.1.4. Valiant Thoracic Stent Graft Usage

All subjects successfully received one (1) or more devices. There were no device malfunctions reported. Thirty-one of the 50 subjects enrolled received a single device. Sixteen of the remaining subjects received two (2) stent grafts and three (3) subjects received three (3) stent grafts at the initial procedure.

Figure 12 below contains the information regarding the average number of devices implanted per subject at initial procedure. Figure 13 provides further information on number of devices implanted to treat the subjects in this study population. A distribution of the type of device components of the Valiant thoracic stent graft configuration implanted is shown in Figure 14 and Figure 15 lists the Core Lab reported length of coverage at baseline.

Figure 12. Number of Devices Implanted at Initial Procedure

16 Instructions for Use English

Figure 13. Proximal Diameters of Implanted Proximal Devices at Initial Procedure

Device Type

% (m/n)1

FreeFlo Straight (Proximal Component) 75.0% (54/72)

Closed Web Straight (Distal Component) 9.7% (7/72)

Distal Bare Spring Straight (Distal Component) 0.0% (0/72)

Closed Web Tapered (Distal Component) 15.3% (11/72)

Based on total number of devices implanted in all subjects

m = number of devices in category, n = total number of devices implanted in all subjects

Figure 14. Devices Implanted by Type at Initial Procedure

Length of Coverage at Baseline

1, 2

(mm)

n 47

Mean ± SD 196.9 ± 67.1

Median 170.9

Min, Max 93, 346

Baseline image is the first post-procedure image.

Based on number of implanted subjects with available data

Core Lab Reported Table

Technical Success

% (m/n)

Vessel Access Success 100.0% (50/50)

Delivery Success 100.0% (50/50)

Deployment Success 100.0% (50/50)

Based on number of ITT subjects with available data

m = number of subjects in category, n = number of subjects with available values

% (m/n)1

Proximal Entry Tear Covered 100.0% (50/50)

Based on number of ITT subjects with available data

m = number of subjects with successful events, n = number of subjects with available values

Entry Tear Coverage

Figure 15. Core Lab Reported Length of Coverage at Baseline

6.1.5. Acute Procedural Data

The technical success was 100%. Vessel access was obtained, the device was successfully delivered and deployed and the proximal entry tear was successfully covered in all subjects, as shown in Figure 16 and Figure 17.

Figure 16. Technical Success

Figure 17. Entry Tear Coverage at Implant

Acute measures at implant are summarized in Figure 18 and Figure 19.

Instructions for Use English 17

18.0% (9/50)

Implant Procedure

% (m/n)

Heparin Administered During Implant

98.0% (49/50)

Type of Anesthesia Used

General

100.0% (50/50)

Spinal

4.0% (2/50)

Epidural

Local

None

40.0% (20/50)

Partial

16.0% (8/50)

Complete

44.0% (22/50)

Subjects with LSA Coverage

LSA Covered Subjects with Any Pre-implant Adjunctive

Procedure

10.0% (3/30)

LSA Covered Subjects with Any Post-implant Adjunctive Procedure

23.3% (7/30)

These included carotid to subclavian bypass, left renal stent, left iliac stent, right iliac stent.

m = number of subjects in category, n = number of subjects with available data. For Subjects with LSA Coverage, the denominator is based on those with LSA coverage or partial coverage.

These included carotid to subclavian bypass, fem fem bypass, SMA stent, left iliac stent, right

iliac stent and other.

0.0% (0/50)

Spinal Protective Measure

LSA Coverage

Spinal CSF Drain

Maintenance of controlled hypertension following placement

Monitoring of evoked potentials

6.0% (3/50)

32.0% (16/50)

54.0% (27/50)

Figure 18. Implant Procedure

18 Instructions for Use English

Acute Measurements at Implant

Duration of Implant Procedure (min)

Mean ± SD

142.9 ± 125.6

Median

108.5

Min, Max

45, 920

Contrast Volume (ml)

Mean ± SD

122.2 ± 72.1

Median

115.0

Min, Max

20, 300

Total Fluoroscopic Time (min)

Mean ± SD

17.1 ± 25.7

Median

12.2

Min, Max

4, 175

Blood Loss During Procedure (ml)

Mean ± SD

180.1 ± 223.6

Median

100.0

Min, Max

10, 1400

Subjects Requiring Blood Transfusion % (m/n)

40.0% (20/50)

Time in ICU (hours)

Mean ± SD

211.4 ± 429.2

Median

76.0

Min, Max

5, 2737

Overall Hospital Stay (days)

Mean ± SD

14.1 ± 19.9

Median

9.0

Min, Max

1, 124

Based on number of ITT subjects with available data

m = number of subjects in category, n = number of subjects with available values

Figure 19. Acute Measurements at Implant

Figure 20 lists the 7 (seven) adjunctive procedures performed prior to and twenty three (23) adjunctive procedures performed after deployment of the study device. Three (3) subjects had an LSA-Carotid bypass procedure before the implant and one (1) subject underwent the bypass as an adjunctive procedure after the implant.

Instructions for Use English 19

Adjunctive Procedures Performed

Prior to

Deployment

% (m/n)

After Deployment

% (m/n)

Based on number of ITT subjects with available data

Based on number of implanted subjects with available data

m = number of subjects in category, n = number of subjects with available data

Thoracentesis/and endoscopy; thrombectomy left common/external IA, interposition graft L CFA;

laparotomy; right common femoral exposure, false lumen thrombectomy and obliteration, patch angioplasty with bovi; endovascular repair of abdominal aortic dissection; right external iliac thrombectomy and stenting and fasciotomy of the right calf; right axilla-femoral bypass and right sided calf fasciotomy

Some subjects had multiple adjunctive procedures.

Intervention location: Aortic arch

Carotid to Subclavian Bypass

Intervention location: Mesenteric vessels

SMA Stent

Intervention location: Renal vessels

Left Renal Stent

Intervention location: Iliac vessels

Left Iliac Stent

Intervention location: Femoral vessels

Fem-Fem Bypass

Right Iliac Stent

Right Renal Stent

Other

No. of Subjects with Adjunctive Procedures

0.0% (0/50)

2.0% (1/50)

6.0% (3/50)

2.0% (1/50)

4.0% (2/50)

0.0% (0/50)

4.0% (2/50)

2.0% (1/50)

0.0% (0/50)

6.0% (3/50)

0.0% (0/50)

2.0% (1/50)

0.0% (0/50)

2.0% (1/50)

16.0% (8/50)

12.0% (6/50)

8.0% (4/50)

6.0% (3/50)

14.0% (7/50)

28.0% (14/50)

Figure 20. Adjunctive Procedures Performed

% (m/n) [95% UCL]

1, 2, 3

30-day All-Cause Mortality 8.0% (4/50) [17.4%]

95% Upper Confidence Limit (UCL) was calculated using an exact method

based on the binomial distribution.

Based on the number of evaluable subjects. Subjects will be considered

unevaluable if they are withdrawn before the lower limit of the 30-day follow-up window (16 days) or they are lost to follow-up before the lower limit of the 30-day follow-up window (16 days) and had no contact thereafter.

Based on CEC adjudicated data

Primary Endpoint

6.1.6. Safety and Effectiveness Results

6.1.6.1. Primary Endpoint Analysis

The primary endpoint for this trial was the all-cause mortality within 30 days of the index procedure. The Medtronic Dissection Trial met its primary endpoint with a 30-day all-cause mortality rate of 8.0%. The upper limit of the one-sided 95.0% confidence interval on the 30-day mortality rate was 17.4%, which was less than the performance goal of 25.0%. Four (4) subjects died within 30 days of the index procedure. Figure 21 lists the site and CEC adjudications for these deaths.

All-cause mortality within 30 Days for subjects with the complicating factor of rupture was 0.0% (0 out of 10 subjects). All-cause mortality within 30 days for subjects with the complicating factor of ischemia only was 10% (4 out of 40 subjects).

20 Instructions for Use English

Figure 21. Primary Endpoint—All-Cause Mortality within 30 Days

Implant to

Death (days)

Cause of Death Site Reported

Death Relatedness

Site Reported

Death Relatedness

CEC Adjudicated

0 Cardiac Tamponade Procedure Related Device Related2,

Procedure Related, Dissection Related

1 Mesenteric Ischemia In

Totalis

Dissection Related Dissection Related

9 Sepsis Not Related Procedure Related,

Dissection Related

26 Pulmonary Embolism Not Related Procedure Related,

Dissection Related

Relationship to Device/Procedure/Dissection

The subject had a large pericardial effusion with acute cardiac tamponade. Underlying

causes/conditions were listed as cardiac arrest, ascending aortic dissection and ascending aortic aneurysm Site and CEC Adjudicated Reported Table

Figure 22. Listing of Deaths

6.1.6.2. Secondary Observations

Figure 23 summarizes the secondary observations in the Medtronic Dissection Trial.

Instructions for Use English 21

Based on number of ITT subjects with available data

Based on the number of evaluable subjects. Subjects will be considered unevaluable if they are withdrawn before the lower limit of the 12 months follow-up window (275 days) or they are lost to follow-up before the lower limit of the 12 months follow-up window (275 days) and had no contact thereafter.

Additional endovascular device placed

LSA plug

Based on CEC adjudicated data

Based on the number of subjects with evaluable imaging at follow-up visit Site Reported and Core Lab Reported Table

100.0% (50/50)

Successful Delivery and Deployment of the Stent Graft

Coverage of Proximal Entry Tear at Implant1

Adverse Events within 30 Days

Non-serious Adverse Events

Device related

Procedure related

Serious Adverse Events

Device related

Dissection related

Procedure related

Dissection related

Rupture within 30 Days

Secondary Procedures within 12 Months

Secondary Endovascular Procedures related to the Dissection

Secondary Endovascular Procedures not related to the Dissection

Open Repair of Retrograde Type A Dissection

Conversion to Open Repair for Descending Dissection

LSA Bypass

Adverse Events within 12 Months

Non-serious Adverse Events

Device related

Procedure related

Serious Adverse Events

Device related

Dissection related

Procedure related

Dissection related

Rupture within 12 Months

All-Cause Mortality within 12 Months

2,5

Continuing or New False Lumen (FL) Perfusion at 6 Month Visit

Core Lab Reported

Continuing or New False Lumen (FL) Perfusion at 12 Month Visit

Core Lab Reported

100.0% (50/50)

16.0% (8/50)

52.0% (26/50)

16.0% (8/50)

0.0% (0/50)

38.0% (19/50)

4.0% (2/50)

20.0% (10/50)

4.0% (2/50)

0.0% (0/50)

28.0% (14/50)

6.3% (3/48)

4.2% (2/48)

2.1% (1/48)

4.2% (2/48)

0.0% (0/48)

16.7% (8/48)

59.2% (29/49)

16.7% (8/48)

0.0% (0/48)

46.9% (23/49)

4.2% (2/48)

20.8% (10/48)

6.3% (3/48)

0.0% (0/48)

34.7% (17/49)

14.6% (7/48)

39.4% (13/33)

27.3% (9/33)

% (m/n)

6.1.6.3. Safety Results: Summary of Adverse Events

Only those adverse events and serious adverse events that were related to the device, to the implant procedure and/or to the aortic disease and serious adverse events that led to death, regardless if they were related to the device, procedure or the aortic disease, were reported by the sites. Thirty eight percent of eligible subjects experienced an SAE within 30 days and 19.6% experienced an SAE between 31 and 365 days. Sixteen percent of eligible subjects experienced an AE (excluding SAEs) within 30 days and 2.2% experienced an AE (excluding SAEs) between 31 and 365 days. Figure 25 through Figure 27 list all adverse events and their relationship to the device, the procedure or the disease, by date of onset. Deaths are listed in Figure 28.

A subject may have experienced multiple adverse events, and in different subcategories; therefore, the number of subjects in each category may not be the sum of those in each subcategory. Each subject was only counted once in each subcategory. An adverse event may have been reported as related to one or more of the following: device, dissection or procedure. In cases where the AE was reported to be related to more than one category, it was included in all applicable AE tables. Therefore, the same event may appear in the device-related, procedure-related or dissection-related SAE tables.

A summary of selected 30-Day SAE results from the Medtronic Dissection Trial and the SVS MAF group is provided in Figure 24.

22 Instructions for Use English

Figure 23. Secondary Observations

Summary of Selected 30 Day SAE Results from Medtronic Dissection Trial and the SVS MAF

Any Event2

Death

Stroke

Respiratory Failure

Paraplegia/Paraparesis

MDT Dissection

Subjects % (m/n)

SVS MAF

Subjects

% (m/n)

37.6% (32/85)

10.6% (9/85)

1.2% (1/85)

9.4% (8/85)

2.4% (2/85)

9.4% (8/85)

m = number of subjects experienced the event in question, n = number of evaluable subjects in the cohort.

A subject may report multiple events; hence, number of subjects with any events may not be the sum of

those in each event.

Includes one event of monoplegia and two events of paraplegia

Each subject was only counted once in each category.

Renal Failure (+ Dialysis)

Bowel Ischemia

9.4% (8/85)

3.5% (3/85)

16.0% (8/50)

8.0% (4/50)

0.0% (0/50)

6.0% (3/50)

0.0% (0/50)

6.0% (3/50)

2.0% (1/50)

Category

0 to 30 Days

% (m/n)

Subjects Experiencing One or More AEs2

4.0% (2/50)

General Disorders And Administration Site Conditions

Continued Perfusion from a Branch Vessel

requiring Treatment

Nervous System Disorders

Cerebrovascular Accident

Vascular Disorders

Retrograde Type A Aortic Dissection

m = number of subjects experiencing one or more device related adverse events in a category, n = number of subjects who experienced a device related adverse event or who died during the interval, or who were followed at least until the lower endpoint of the interval.

A subject may report multiple adverse events and in different categories; hence, number of subjects in each category may not be the sum of those in each subcategory. Each subject was only counted once in each subcategory and category.

0.0% (0/50) 0.0% (0/46)

2.2% (1/46)

31 to 365 Days

% (m/n)

0 to 30 Days

% (m/n)

31 to 365 Days

% (m/n)

SAE AE (Non-Serious)

2.0% (1/50)

A comparison of rates of particular 30-day SAEs provided in the SVS MAF to those in the Medtronic Dissection Trial is presented in Figure 24. Overall, 30-day SAE rates in the Medtronic Dissection Trial group were comparable to or lower than those in the SVS MAF group. Stroke was reported in three (3) subjects in the Medtronic Dissection Trial group. One resolved without treatment and two were unresolved at the time of the patients' deaths. Paralysis was reported in three (3) subjects. One was unresolved at the time of the patient's death, one resulted in above the knee amputation and remained unresolved and one remains unresolved and is not being treated any further by the physician.

Figure 24. Selected 30-Day SAE Results from Medtronic Dissection Trial and SVS MAF Group

Device related adverse events

Device-related AEs and SAEs are listed in Figure 25. Four (4) percent of eligible subjects experienced a device-related AE/SAE within 30 days whereas 2.2% experienced a devicerelated AE/SAE between 31 and 365 days.

Three (3) serious adverse events were reported as related to the device: retrograde Type A aortic dissection, CVA and continued perfusion from a branch vessel.

Figure 25. Subjects with Device Related Adverse Events by Date of Onset

Procedure related adverse events

Procedure related adverse events are listed in Figure 26. Thirty-four percent of eligible subjects experienced a procedure-related AE/SAE within 30 days whereas 4.3% experienced a procedure-related AE/SAE between 31 and 365 days. The following procedure-related adverse events which were observed in the trial are considered to be of greatest importance with endovascular treatment: cerebral ischemia (narrowing of a vessel seen on imaging), CVA (infarct due to a blocked vessel), monoplegia, spinal cord ischemia, intermittent claudication and seroma. None of these occurred at rates that were unexpected or that were outside those reported in the literature.

Instructions for Use English 23

0 to 30 Days

% (m/n)

31 to 365 Days

% (m/n)

0 to 30 Days

% (m/n)

31 to 365 Days

% (m/n)

SAE AE (Non-Serious)

2.0% (1/50)

6.0% (3/50)

2.0% (1/50)

10% (5/50)

2.0% (1/50)

6.0% (3/50)

2.0% (1/50)

6.0% (3/50)

20.0% (10/50)

2.0% (1/50)

m = number of subjects experiencing one or more procedure related adverse events in a category, n = number of subjects who experienced a

procedure related adverse event or who died during the interval, or who were followed at least until the lower endpoint of the interval.

A subject may report multiple adverse events and in different categories; hence, number of subjects in each category may not be the sum of

those in each subcategory. Each subject was only counted once in each subcategory and category.

-- --

2.0% (1/50)

Category

Subjects Experiencing One or More AEs

Blood And Lymphatic System Disorders

Haemorrhagic Anaemia

Heparin-Induced Thrombocytopenia

Cardiac Disorders

Cardiac Tamponade

General Disorders And Administration Site Conditions

Malaise

Infections And Infestations

Pneumonia

Urinary Tract Infection

Procedural Complications

Incision Site Pain

Nerve Injury

Seroma

Stent-Graft Endoleak

2.0% (1/50)

4.0% (2/50)

16.0% (8/50) 2.2% (1/46)

Wound

Metabolism And Nutrition Disorders

Hyperglycaemia

Musculoskeletal And Connective Tissue Disorders

Back Pain

Pain In Extremity

Rhabdomyolysis

Nervous System Disorders

Cerebral Ischaemia

Cerebrovascular Accident

Headache

Monoplegia

Transient Spinal Cord Ischaemia

2.0% (1/50)

2.2% (1/46)

4.0% (2/50)

2.0% (1/50)

Respiratory, Thoracic And Mediastinal Disorders

Pleural Effusion

Pulmonary Oedema

Respiratory Failure

Skin And Subcutaneous Tissue Disorders

Skin Ulcer

6.0% (3/50)

2.0% (1/50)

4.0% (2/50)

2.0% (1/50)

-- --

Vascular Disorders

Deep Vein Thrombosis

Haemorrhage

Intermittent Claudication

Subclavian Artery Embolism

-- -- --

2.0% (1/50)

2.2% (1/46)

Figure 26. Subjects with Procedure Related Adverse Events by Date of Onset

24 Instructions for Use English

Dissection related adverse events

Dissection related adverse events are listed in Figure 27. Thirty percent of eligible subjects experienced a dissection-related AE/SAE within 30 days whereas 10.9% experienced a dissection-related AE/SAE between 31 and 365 days. Retrograde Type A dissection was reported in one subject on day 5 and in another subject on day 56 post-procedure. Both subjects underwent open repair the following day, resolving the SAE. Stroke was reported in two (2) subjects. In one subject, it occurred on day 1 post-procedure and was unresolved at the time of the patient's death. In the second subject it occurred on day 7 and was resolved without treatment. Paralysis was reported in three (3) subjects. One was unresolved at the time of the patient's death, one resulted in above the knee amputation and remained unresolved and one remains unresolved and is not being treated any further by the physician.

Instructions for Use English 25

0 to 30 Days

% (m/n)

31 to 365 Days

% (m/n)

0 to 30 Days

% (m/n)

31 to 365 Days

% (m/n)

SAE AE (Non-Serious)

4.0% (2/50)

2.0% (1/50)

4.0% (2/50)

2.0% (1/50)

6.0% (3/50)

2.0% (1/50)

28.0% (14/50)

m = number of subjects experiencing one or more procedure related adverse events in a category, n = number of subjects who experienced a

dissection related adverse event or who died during the interval, or who were followed at least until the lower endpoint of the interval.

A subject may report multiple adverse events and in different categories; hence, number of subjects in each category may not be the sum of

those in each subcategory. Each subject was only counted once in each subcategory and category.

Listed as dissection-related as per site reports.

2.2% (1/46)

2.0% (1/50)

2.2% (1/46)

8.7% (4/46)

-- --

2.2% (1/46)

2.0% (1/50)

4.3% (2/46)

Category

Subjects Experiencing One or More AEs

Gastrointestinal Disorders

Ileus

Intestinal Ischaemia

General Disorders And Administration Site Conditions

Malaise

Continued Perfusion from a Branch Vessel requiring Treatment

Procedural Complications

Nerve Injury

Stent-Graft Endoleak

Weight Decreased

4.0% (2/50) 2.2% (1/46)

White Blood Cell Count Increased

Musculoskeletal And Connective Tissue Disorders

Muscular Weakness

Pain In Extremity

Rhabdomyolysis

Nervous System Disorders

Cerebral Ischaemia

Cerebrovascular Accident

Depression

Monoplegia

Psychiatric Disorders

Paralysis

Mental Status Changes

Renal And Urinary Disorders

Renal Failure Acute

Respiratory, Thoracic And Mediastinal Disorders

Haemothorax

Vascular Disorders

Aortic Aneurysm

2.0% (1/50)

8.0% (4/50)

2.0% (1/50)

Aortic Disorder

Retrograde Type A Aortic Dissection

Haemorrhage

Hypertension

Peripheral Arterial Occlusive Disease

-- -- --

2.0% (1/50)

10.9% (5/46)

Abnormal Lab Values

Peripheral Vascular Disorder

Subclavian Artery Embolism

2.0% (1/50)

4.0% (2/50)

2.0% (1/50)

2.2% (1/46)

4.0% (2/50)

Paraplegia

10.0% (5/50)

2.2% (1/46)

2.0% (1/50)

2.2% (1/46)

26 Instructions for Use English

Figure 27. Subjects with Dissection Related Adverse Events by Date of Onset

All cause mortality

Implant to

Death (days)

Cause of Death Site Reported

Death Relatedness1 Site Reported

Death Relatedness1 CEC Adjudicated

0 Cardiac Tamponade2 Procedure Related Device Related,

Procedure Related, Dissection Related

1 Mesenteric Ischemia In

Totalis3

Dissection Related Dissection Related

9 Sepsis4 Not Related Procedure Related,

Dissection Related

26 Pulmonary Embolism5 Not Related Procedure Related,

Dissection Related

71 Cardiac Arrest

Not Related Not Related

87 Pneumonia

Not Related Dissection Related

124 Cardiac Arrest

Not Related Procedure Related

432 Natural Causes

Not Related Not Related

Relationship to Device/Procedure/Dissection

The subject had a large pericardial effusion with acute cardiac tamponade most likely due to injury by a guidewire or catheter. Underlying causes /conditions were listed as cardiac arrest, ascending aortic dissection and ascending aortic aneurysm.

The subject was diagnosed with mesenteric ischemia in totalis. Immediate cause of death was identified as multi-system organ failure due to or as a consequence of an acute complicated Type B dissection.

The subject's immediate cause of death was sepsis, with contributing causes listed as pneumonia, respiratory failure and descending aortic aneurysm. In addition, CT data was suggestive of a stroke. See Figure 24 for additional information.

The subject had pulmonary embolism due to or as a consequence of a DVT and AAA repaired with stents.

The subject had a sudden cardiac arrest in spite of gradual improvement following treatment.

The subject experienced fever, abdominal pain and abnormal LFTs prior to death whose cause was reported to be pneumonia.

The subject's immediate cause of death was identified as cardiac arrest due to or as a consequence of abdominal sepsis with a contributing cause of sacral decubitus ulcer.

In addition to aortic dissection, the subject experienced CHF, COPD, DVT and RA. Site and CEC Adjudicated Reported Table

6.1.6.4. Effectiveness Results

To assess the performance of the Valiant thoracic stent graft, the Medtronic Dissection Trial collected information on the secondary observations (Figure 23) along with the following additional device assessments:

•

False lumen thrombosis and aortic remodeling were reported in three sections: the stented segment, the bottom of the stent to the celiac artery and the celiac artery to the aortic bifurcation. In addition, the volumes and diameters of the false and true lumens were measured over the entire aorta (from LSA to aortic bifurcation). Baseline measurements were obtained from the first post-operative images, not from pre-treatment images.

False lumen thrombosis status: Over the stented aortic segment, the core lab reported partial or complete thrombosis of the false lumen in 87.5% of the subjects at the first postprocedural CT (partial in 45.0% and complete in 42.5%). This number increased to 90.9% of the subjects at the 12-month visit (partial in 18.2% and complete in 72.7%). Thrombosis status reported by the sites indicated 65.1% of the subjects had a partially or a completely thrombosed false lumen at the first post-procedural CT (partial in 30.2% and complete in

34.9%). The percentage remained high at more than 79% at the 12-month visit (partial in 14.7% and complete in 64.7%). Over the remaining segments, both the core lab and the sites reported a positive trend towards partial or complete thrombosis. Thirty five of the 49 subjects (in whom the data was available) had a dissection that extended to or past the aortic bifurcation into the iliac or femoral arteries. Among these subjects,

18 had at least one re-entry tear and 10 had three or more re-entry tears. This may have contributed to the false lumen remaining patent in a higher percentage of subjects outside the stented region.

False lumen thrombosis status

Aortic remodeling

Endoleaks

Technical observations at follow-up

Figure 28. Listing of Deaths

Instructions for Use English 27

Thrombosis Status1

Baseline2

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month

Follow-up

% (m/n)

Stented Segment

Patent

12.5% (5/40)

3.0% (1/33)

9.1% (3/33)

Partially Thrombosed

45.0% (18/40)

36.4% (12/33)

18.2% (6/33)

Thrombosed

42.5% (17/40)

60.6% (20/33)

72.7% (24/33)

Based on number of ITT subjects with available data

Baseline image is the first post-procedure image

m = number of subjects in category, n = number of subjects with available values Core Lab reported data

Figure 29. Core Lab Reported False Lumen Thrombosis Status, Stented Segment

Thrombosis Status1

Baseline2

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month

Follow-up

% (m/n)

Stented Segment

Patent

34.9% (15/43)

24.2% (8/33)

20.6% (7/34)

Partially Thrombosed

30.2% (13/43)

30.3% (10/33)

14.7% (5/34)

Thrombosed

34.9% (15/43)

45.5% (15/33)

64.7% (22/34)

Based on number of ITT subjects with available data

Baseline image is the first post-procedure image

m = number of subjects in category, n = number of subjects with available values

Figure 30. Site Reported False Lumen Thrombosis Status, Stented Segment

Aortic Remodeling: The trial data demonstrated favorable remodeling of the stented segment of the aorta after TEVAR. Beyond the stented segment, a trend towards positive remodeling was seen.

Over the stented aortic segment, both the sites and the core lab reported that the true lumen diameter remained stable or increased (by at least 5.0 mm) compared to baseline in more than 90% of the subjects and that the false lumen remained stable or decreased (by at least 5.0 mm) compared to baseline in at least 75% of the subjects at the 12-month visit. The sites and the core lab reported that the total aortic diameter remained either stable or decreased (by at least 5.0 mm) compared to baseline in 85.3% (site reported) and 78.1% (core lab reported) of the subjects at the 12-month visit.

28 Instructions for Use English

Thoracic Dissection Measurements1

Baseline2

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month Follow-up

% (m/n)

Change from Baseline2 in the Maximum True Lumen Diameter over the Length of the Stent Graft

Decrease3

6.7% (2/30)

6.9% (2/29)

Stable

60.0% (18/30)

58.6% (17/29)

Increase

33.3% (10/30)

34.5% (10/29)

Change from Baseline2 in the Maximum False Lumen Diameter over the Length of the Stent Graft

Decrease3

40.0% (12/30)

44.8% (13/29)

Stable

46.7% (14/30)

31.0% (9/29)

Increase

13.3% (4/30)

24.1% (7/29)

Change from Baseline2 in the Maximum Total Descending Thoracic Aortic Diameter (mm)

Decrease3

18.2% (6/33)

25.0% (8/32)

Stable

63.6% (21/33)

53.1% (17/32)

Increase

18.2% (6/33)

21.9% (7/32)

False Lumen Thrombosis over the Length of the Stent Graft

Completely Thrombosed

42.5% (17/40)

60.6% (20/33)

72.7% (24/33)

Partially Thrombosed

45.0% (18/40)

36.4% (12/33)

18.2% (6/33)

Patent

12.5% (5/40)

3.0% (1/33)

9.1% (3/33)

Based on number of ITT subjects with available data

Baseline image is the first post-procedure image

Decrease is defined as a 5mm or greater decrease from baseline in measured diameter, increase is defined as a 5mm or greater increase from baseline in measured diameter m = number of subjects in category, n = number of subjects with available values Core Lab Reported Table

Figure 31. Core Lab Reported Aortic Remodeling Based on 5mm Change

Instructions for Use English 29

Thoracic Dissection Measurements1

Baseline2

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month Follow-up

% (m/n)

Change from Baseline2 in the Maximum True Lumen Diameter over the Length of the Stent Graft

Decrease3

6.1% (2/33)

5.9% (2/34)

Stable

54.5% (18/33)

47.1% (16/34)

Increase

39.4% (13/33)

47.1% (16/34)

Change from Baseline2 in the Maximum False Lumen Diameter over the Length of the Stent Graft

Decrease3

36.4% (12/33)

50.0% (17/34)

Stable

39.4% (13/33)

32.4% (11/34)

Increase

24.2% (8/33)

17.6% (6/34)

Change from Baseline2 in the Maximum Total Descending Thoracic Aortic Diameter (mm)

Decrease3

35.3% (12/34)

32.4% (11/34)

Stable

41.2% (14/34)

52.9% (18/34)

Increase

23.5% (8/34)

14.7% (5/34)

False Lumen Thrombosis over the Length of the Stent Graft

Completely Thrombosed

34.9% (15/43)

45.5% (15/33)

64.7% (22/34)

Partially Thrombosed

30.2% (13/43)

30.3% (10/33)

14.7% (5/34)

Patent

34.9% (15/43)

24.2% (8/33)

20.6% (7/34)

Based on number of ITT subjects with available data

Baseline image is the first post-procedure image

Figure 32. Site Reported Aortic Remodeling Based on 5mm Change

Change in True and False Lumen Volume: The volumes of the false and true lumens were measured by the core lab over the entire aorta (from LSA to aortic bifurcation) and in the three aortic segments described above. Volume expansion of the true lumen over the length of the stented segment was observed in 100% of evaluable subjects at 12 months. The true lumen volumes over the other segments and over the entire aorta followed similar trends in that each remained stable or increased in more than 84% of evaluable subjects at the 12-month visit. Over the length of the stented segment, volume regression of the false lumen was observed in 94.4% of evaluable subjects at 12 months. Over the other segments and over the entire aorta (from the LSA to the aortic bifurcation), a trend toward volume regression of the false lumen was observed.

30 Instructions for Use English

Change in False and True Lumen Volume1

6 Month Change

from Baseline2

% (m/n)

12 Month Change

from Baseline2

% (m/n)

False Lumen (FL)

FL Volume from LSA to Aortic Bifurcation

Decrease3

56.5% (13/23)

61.9% (13/21)

Stable

8.7% (2/23)

19.0% (4/21)

Increase

34.8% (8/23)

19.0% (4/21)

FL Volume of Stented Segment (V1)

Decrease3

85.0% (17/20)

94.4% (17/18)

Stable

Increase

15.0% (3/20)

5.6% (1/18)

FL Volume Aortic Segment Stent to Celiac Artery (V2)

Decrease3

61.9% (13/21)

77.3% (17/22)

Stable

9.5% (2/21)

13.6% (3/22)

Increase

28.6% (6/21)

9.1% (2/22)

FL Volume Aortic Segment Celiac Artery to Bifurcation (V3)

Decrease3

30.4% (7/23)

36.4% (8/22)

Stable

13.0% (3/23)

13.6% (3/22)

56.5% (13/23)

50.0% (11/22)

True Lumen (TL)

TL Volume from LSA to Aortic Bifurcation

Decrease3

4.2% (1/24)

Stable

7.7% (2/26)

8.3% (2/24)

Increase

92.3% (24/26)

87.5% (21/24)

TL Volume of Stented Segment (V1)

Decrease3

Stable

3.4% (1/29)

Increase

96.6% (28/29)

100.0% (29/29)

TL Volume Aortic Segment Stent to Celiac Artery (V2)

Decrease3

8.0% (2/25)

16.0% (4/25)

Stable

8.0% (2/25)

4.0% (1/25)

Increase

84.0% (21/25)

80.0% (20/25)

TL Volume Aortic Segment Celiac to Bifurcation (V3)

Decrease3

11.1% (3/27)

12.0% (3/25)

Stable

66.7% (18/27)

36.0% (9/25)

22.2% (6/27) 52.0% (13/25)

Increase

Based on number of ITT subjects with available data

Baseline image is the first post-procedure image

Decrease is defined as a 10% or greater decrease from baseline in measured volume, increase is defined as a 10% or greater increase from baseline in measured volume m = number of subjects in category, n = number of subjects with available values Core Lab Reported Table

Increase

0.0% (0/20) 0.0% (0/18)

0.0% (0/26)

0.0% (0/29) 0.0% (0/29)

0.0% (0/29)

Figure 33. Core Lab Reported 10% Change in False and True Lumen Volumes

Endoleaks: A summary of the endoleaks reported by both the sites and the core lab from implant through 12 months is reported in Figure 34 and Figure 35.

Instructions for Use English 31

Endoleaks1

Discharge Follow-up

% (m/n)

1-Month

Follow-up

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month

Follow-up

% (m/n)

Type Ia (proximal end)

6.1% (2/33)

Type Ib (distal end)

Type II

Type III

Type IV

Endoleak Type Undetermined

3.0% (1/33)

Based on number of implanted subjects with available data

m = number of subjects in category, n = number of subjects with available values Core Lab Reported Table

0.0% (0/34)

0.0% (0/39)

0.0% (0/33)

Figure 34. Core Lab Reported Endoleaks

Endoleaks1

Based on number of implanted subjects with available data

Unresolved endoleaks only

m = number of subjects in category, n = number of subjects with available values

0.0% (0/33)

0.0% (0/50)

6.0% (3/50)

Procedure

% (m/n)

3.0% (1/33)

6.1% (2/33)

Discharge Follow-up

% (m/n)

2.5% (1/40)

1-Month

Follow-up

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month

Follow-up

% (m/n)

3.1% (1/32)

3.0% (1/33)

0.0% (0/32)

0.0% (0/34)

0.0% (0/40)

10.0% (4/40)

Type Ia (proximal end)

Type Ib (distal end)

Type II

Type III

Type IV

Endoleak Type Undetermined

Evidence of Misaligned Deployment

Stent Graft Fracture

Loss of Integrity

Loss of Patency

Migration > 10mm from Baseline2

Proximal Migration

Distal Migration

Discharge Follow-up

% (m/n)

1-Month

Follow-up

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month Follow-up

% (m/n)

0.0% (0/38)

0.0% (0/37)

0.0% (0/33)

0.0% (0/46)

0.0% (0/45)

0.0% (0/40)

0.0% (0/33)

0.0% (0/34)

0.0% (0/33)

0.0% (0/34)

Based on number of ITT subjects with available data

Baseline image is the first post-procedure image m = number of subjects in category, n = number of subjects with available values

Technical Observations

Stent Graft Kinking

Stent Graft Twisting

Figure 35. Site Reported Endoleaks

Technical observations at follow-up: Imaging for subjects that completed the discharge, one-month, six-month and twelve-month follow-up intervals were reviewed for technical observations by both the core lab and the sites. The stent graft maintained patency and integrity at all of the time intervals. In addition, there was no evidence of misaligned deployment, stent graft twisting, stent graft kinking, or stent graft fracture. Site reported and core lab technical observations by device imaging assessment are listed in Figure 36 and Figure 37.

32 Instructions for Use English

Figure 36. Site Reported Technical Observations by Device Imaging Assessments

Technical Observations

1,2

Stent Graft Kinking

Stent Graft Twisting

Stent Graft Fracture

Loss of Integrity

Loss of Patency

Discharge Follow-up

% (m/n)

1-Month

Follow-up

% (m/n)

6-Month

Follow-up

% (m/n)

12-Month Follow-up

% (m/n)

Based on number of ITT subjects with available data

No current definition for Migration in a dissection population has been published. The Core Lab and the Sponsor have agreed that the migration

definition for an aneurysm population is not appropriate, therefore migration has not been reported in this table. m = number of subjects in category, n = number of subjects with available values Core Lab Reported Table

0.0% (0/8)

0.0% (0/7)

0.0% (0/34)

0.0% (0/39)

0.0% (0/38)

0.0% (0/32)

0.0% (0/39)

0.0% (0/26)

0.0% (0/24)

0.0% (0/33)

0.0% (0/27)

0.0% (0/32)

Figure 37. Core Lab Reported Technical Observations by Device Imaging Assessments

6.1.7. Data Post 12 Months

As of the data cut-off date (May 30, 2013), seventeen subjects (17) had been followed through 2 years and one (1) subject has been followed through 3 years. Twenty three (23) subjects had not reached their 2-year visit. One (1) subject died on day 432 due to natural causes. The death was adjudicated by the CEC to be not related to the device, procedure or dissection. No ruptures, conversions to surgical repair, stent graft occlusions, or SAEs related to the device, procedure or aortic disease have been reported past 12 months. In one (1) subject, the site reported an endoleak, type undetermined. One subject underwent an additional endovascular procedure for continued perfusion of the false lumen, at which time two (2) additional stent grafts were implanted. The site reported the event as resolved at the time of the data cut-off for this summary.

6.1.8. Overall Conclusions

The Medtronic Dissection Trial met its primary endpoint with a 30-day all-cause mortality rate of 8.0%. In addition, the overall outcomes measured in terms of secondary observations were commensurate with those reported in the published literature. Based on the data collected and presented, there is reasonable assurance of safety and effectiveness of the Valiant thoracic stent graft in the treatment of Type B dissection for subjects who have appropriate vascular anatomy and who are candidates for endovascular treatment.

6.2. RESCUE

The RESCUE study (G090201) was a prospective, non-randomized, multicenter study to evaluate the clinical performance of the Valiant thoracic stent graft for treatment of blunt thoracic aortic injury (BTAI). The primary objective was to evaluate the safety and effectiveness of the Valiant thoracic stent graft in the treatment of BTAI as determined by all-cause mortality within 30-days of the index procedure. CT images through 12 months will be evaluated by the sites and by an independent Core Lab. Site data will be used for reporting purposes at 2, 3, 4 and 5 years. Chest x-rays were evaluated by the sites and Core Lab at 1 year and will be evaluated by the sites at 3 and 5 years. All deaths were reviewed and adjudicated by an independent Clinical Events Committee (CEC), and will continue to be reviewed and adjudicated through 5 years. An independent Data Monitoring Committee (DMC) met to review trial conduct and study data after the first 20 subjects reached the 30-day follow-up time point and recommended that the clinical trial continue without modifications.

6.2.1. Clinical Endpoints

The primary safety endpoint was all-cause mortality within 30 days of the index procedure. Additional secondary objectives evaluated the acute and long term safety and effectiveness by reporting the following outcomes within 30 days: aortic related mortality, device, procedure and aortic related adverse event and successful delivery and deployment of the stent graft.

The primary objective and set of secondary objectives were assessed descriptively and there was no formal hypothesis testing. The sample size of 50 subjects was planned without a formal statistical sample size calculation and selected based on precision around the estimated 30-day mortality.

6.2.2. Accountability of PMA Cohort

Fifty subjects (50) were enrolled in this study between April 2010 and January 2012 at 20 investigational sites. All enrolled subjects underwent endovascular repair with the Valiant thoracic stent graft. Figure 38 summarizes the subject accountability and compliance by study interval.

Instructions for Use English 33

Subject Follow-up

% (m/n)2

Subject Imaging

% (m/n)2

Patients with Adequate

Imaging to Assess the

Parameter

% (m/n)

Subject Accountability

Implant and

Follow-up

Eligible

Clinical

Follow-

Imaging

Follow-

CT/MR

Imaging

Chest

X-Ray

Additional

Imaging

Modalities

Endoleak

Migration

from 1 Month

Integrity

Enrolled

but not

Implanted

Withdrawal

Conversion

to Surgery

Death

Lost to

Follow-

Not Due for Next

Visit

Implant

Events

Between

Implant and

1-Month

0 0 0 4

0 0

1-Month

97.9%

(46/47)

95.7%

(45/47)

95.7%

(45/47)

0.0%

(0/47)

93.6%

(44/47)

97.9%

(46/47)

Events

Between

1-Month and

6-Month

0 0 13 0 18

6-Month

85.2%

(23/27)

81.5%

(22/27)

81.5%

(22/27)

0.0%

(0/27)

81.5%

(22/27)

81.5%

(22/27)

81.5%

(22/27)

Events

Between

6-Month and

12-Month

0 0 0 0 13

12-Month

85.7%

(12/14)

85.7%

(12/14)

85.7%

(12/14)

85.7%

(12/14)

0.0%

(0/14)

85.7%

(12/14)

85.7%

(12/14)

85.7%

(12/14)

Events

Between 12-

Month and

2-Year

0 0 0 0 14

2-Year

0.0% (0/0)

Total

0 0 0 5 0

Deaths Post Conversion to Surgery

Total Deaths

Eligible at implant are all subjects enrolled by snapshot date. Eligible (ET) for time intervals post implant is eligible from the previous interval (EPI) less the sum of enrolled but not implanted (ENI) plus withdrawal (W) plus conversion to surgery (CTS) plus death (D) plus lost to follow-up (LTF) plus not due for next visit (NDNV) subjects. ET = EPI – (ENI + W + CTS + D + LTF + NDNV).

Percentages are based on number of all subjects enrolled by snapshot date and include subjects that have a completed clinical/imaging follow-up form for the time point, divided by number of eligible subjects. To be considered within window, a subject must have at a minimum, the clinical follow up or the imaging follow-up occurring within the follow-up window.

There were four (4) deaths within 30-days and 47 subjects were eligible at 1-month follow-up visit instead of 46 subjects since one subject that died had completed the 1-month follow-up visit prior to death. This subject is included under the eligible subjects at 1-month follow-up time point in the table m = number of subjects in category, n = number of subjects with available data. Site Reported Table.

6.2.3. Subject Population Demographics and Baseline Parameters

Figure 39 through Figure 43 provide baseline parameters of the study subjects including demographics, medical history, associated injuries to the BTAI, pre-treatment risk using the injury severity score (ISS), and radiological aortic assessment.

Figure 38. RESCUE Trial Subject Follow-up, Imaging and Accountability

34 Instructions for Use English

Age (years)

n 50

Mean ± SD 40.7 ± 17.4

Median 39.5

Min, Max 18, 76

Sex % (m/n)

Male 76.0% (38/50)

Female 24.0% (12/50)

Ethnicity % (m/n)

Hispanic or Latino 20.0% (10/50)

Not Hispanic or Latino 72.0% (36/50)

Not Available 8.0% (4/50)

Race % (m/n)

White 68.0% (34/50)

Black or African American 20.0% (10/50)

Asian 4.0% (2/50)

Native Hawaiian or Other Pacific Islander 0.0% (0/50)

American Indian or Alaska Native 0.0% (0/50)

Other 4.0% (2/50)

Not Available 4.0% (2/50)

m = number of subjects in category, n = number of subjects enrolled in this study. Site Reported Table.

Weight (lbs)

n 50

Mean ± SD 189.3 ± 39.3

Median 186.1

Min, Max 115, 324

Figure 39. Subject Demographic

Instructions for Use English 35

Subject Injury Characteristics

Duration from Injury to Procedure (days)

n 50

Mean ± SD 1.8 ± 4.0

Median 1.0

Min, Max 0, 23

Assigned ISS

n 50

Mean ± SD 37.6 ± 14.3

Median 35.0

Min, Max 13, 75

Mechanism of Blunt Injury % (m/n)

Motor Vehicle Accident 60.0% (30/50)

Motorcycle Accident 22.0% (11/50)

Pedestrian Hit by Motor Vehicle 10.0% (5/50)

Fall 4.0% (2/50)

Other 4.0% (2/50)

Associated Traumatic Injuries % (m/n)

Head Injury 48.0% (24/50)

Long Bone Fracture 38.0% (19/50)

Pelvic Fracture 40.0% (20/50)

Scapula Fracture 8.0% (4/50)

Unstable C/T/L Spine Fractures 14.0% (7/50)

Abdominal Injury (solid organ, bowel, bladder, or diaphragm injury) 58.0% (29/50)

Lung Injury 70.0% (35/50)

Neurologic Deficits 12.0% (6/50)

Rib Fracture 64.0% (32/50)

Sternum Fracture 6.0% (3/50)

Other 50.0% (25/50)

Location of Aortic Injury % (m/n)

Isthmus (just distal to the left subclavian artery to the third intercostals artery) 84.0% (42/50)

Distal Descending Thoracic Aorta 16.0% (8/50)

Extent of Aortic Injury % (m/n)1

Grade 1 - Intimal Tear 18.0% (9/50)

Grade 2 - Intramural Hematoma 12.0% (6/50)

Grade 3 - Aortic Pseudoaneurysm 68.0% (34/50)

Grade 4 - Free Rupture 2.0% (1/50)

m = number of subjects in category, n = number of subjects enrolled in this study. Site Reported Table.

Azizzadeh A, Keyhani K, Miller CC, Coogan SM, Safi HJ, Estrera AL: Blunt traumatic aortic injury: Initial experience with

endovascular repair. J Vasc Surg 2009; 49: 1403-8.

Figure 40. Subject Injury Characteristics

36 Instructions for Use English

Thoracic Aortic Measurements: Diameters (mm)

D1: Aortic Diameter at Left Common Carotid Artery

n 50

Mean ± SD 24.2 ± 5.0

Median 24.0

Min, Max 10, 40

D2: Aorta Diameter (2 cm proximal to injury)

n 50

Mean ± SD 24.3 ± 3.9

Median 23.5

Min, Max 18, 35

D3: Maximum Descending Thoracic Aorta Diameter

n 50

Mean ± SD 26.5 ± 6.6

Median 25.5

Min, Max 18, 42

D4: Aorta Diameter (2 cm distal to the injury)

n 50

Mean ± SD 22.5 ± 4.1

Median 21.0

Min, Max 18, 34

D5: Aortic Diameter at Celiac Axis

n 491

Mean ± SD 20.5 ± 3.5

Median 20.0

Min, Max 14, 28

Right Common Iliac Diameter

n 491

Mean ± SD 10.0 ± 1.7

Median 10.0

Min, Max 6, 13

Left Common Iliac Diameter

n 491

Mean ± SD 10.0 ± 1.8

Median 10.0

Min, Max 6, 15

Right External Iliac Diameter

n 491

Mean ± SD 8.1 ± 1.5

Median 8.0

Min, Max 3, 11

Left External Iliac Diameter

n 491

Mean ± SD 8.1 ± 1.7

Median 8.0

Min, Max 3, 12

Right Femoral Diameter

n 472

Mean ± SD 8.2 ± 1.4

Median 8.0

Min, Max 5, 13

Left Femoral Diameter

n 472

Mean ± SD 8.0 ± 1.6

Median 8.0

Min, Max 4, 14

The images taken for some subjects did not cover the celiac axis region.

There were three cases in which the pre-implant image was insufficient and the access was assessed during the procedure. There were no access issues or any adverse events related to the procedure in these subjects. Site Reported Table.

Figure 41. Site Reported Thoracic Aortic Measurements - Diameters

Instructions for Use English 37

Subject Medical History % (m/n)

Hypertension

Yes 24.0% (12/50)

No 74.0% (37/50)

Unknown 2.0% (1/50)

COPD

Yes 4.0% (2/50)

No 94.0% (47/50)

Unknown 2.0% (1/50)

Congestive Heart Failure

Yes 2.0% (1/50) No 96.0% (48/50)

Unknown 2.0% (1/50)

Paraplegia

Yes 2.0% (1/50) No 96.0% (48/50)

Unknown 2.0% (1/50)

Diabetes

Yes 2.0% (1/50) No 96.0% (48/50)

Unknown 2.0% (1/50)

GI Conditions

Yes 2.0% (1/50)

No 94.0% (47/50)

Unknown 4.0% (2/50)

Yes 0.0% (0/50) No 98.0% (49/50)

Unknown 2.0% (1/50)

Coronary Artery Bypass Grafting (CABG)

Yes 0.0% (0/50)

No 98.0% (49/50)

Unknown 2.0% (1/50)

Renal Insufficiency

Yes 0.0% (0/50)

No 98.0% (49/50)

Unknown 2.0% (1/50)

Stroke/Cerebrovascular Accident (CVA)

Yes 0.0% (0/50)

No 98.0% (49/50)

Unknown 2.0% (1/50)

Paraparesis

Yes 0.0% (0/50)

No 98.0% (49/50)

Unknown 2.0% (1/50)

Bleeding Disorder

Yes 0.0% (0/50)

No 98.0% (49/50)

Unknown 2.0% (1/50)

Other Important Medical Conditions

Yes 46.0% (23/50)

No 54.0% (27/50)

m = number of subjects in category, n = number of intent to treat (ITT) subjects enrolled in this study. Site Reported Table.

38 Instructions for Use English

Figure 42. Subject Medical History

Thoracic Measurements: Lengths (mm)

L1: Distance from LCC to Injury (pre-implant)

n 50

Mean ± SD 30.0 ± 8.2

Median 29.5

Min, Max 20, 52

L2: Distance from LSA to Injury (pre-implant)

n 50

Mean ± SD 15.0 ± 9.4

Median 13.5

Min, Max 0, 36

L3: Distance from Injury to Celiac Axis (pre-implant)

n 421

Mean ± SD 175.1 ± 50.9

Median 182.5

Min, Max 17, 300

The images taken for some subjects did not cover the celiac axis region.

Site Reported Table.

Figure 43. Thoracic Measurements - Lengths

Number of Devices Implanted1

Subjects

% (m/n)

1 96.0% (48/50)

2 4.0% (2/50)

Number of devices implanted includes devices implanted at initial procedure.

One subject had one Talent Thoracic Stent Graft implanted distal to the Valiant Thoracic Stent Graft. m = number of subjects in category, n = number of subjects enrolled in this study. Site Reported Table.

Valiant Device Diameter

Number of Devices

Implanted

22 11

24 8

26 8

28 11

30 6

32 1

34 3

36 2

38 1

40 0

42 0

44 0

Site Reported Table.

Length of Coverage (post-implant) (mm)

n 451

Mean ± SD 130.4 ± 21.3

Median 136.2

Min, Max

This is core lab reported data. Core lab did not receive adequate imaging from all sites.

Core Lab Reported Table.

90, 179

6.2.4. Valiant Thoracic Stent Graft Usage

Information regarding numbers and sizes of devices are presented in Figure 44 through Figure 46.

Figure 44. Number of Devices Implanted

Figure 45. Proximal Valiant Device Diameters Implanted at Initial Procedure

6.2.5. Acute Procedural Data

Vessel access was obtained in all subjects and the device was successfully delivered and deployed in all the subjects in this study population as shown in Figure 47.

Figure 46. Length of Stent Graft Coverage

Instructions for Use English 39

Technical Success % (m/n)

Vessel Access Success 100.0% (50/50)

Delivery Success 100.0% (50/50)

Deployment Success 100.0% (50/50)

m = number of subjects in category, n = number of subjects enrolled in this study. Site Reported Table.

Figure 47. Technical Success

% (m/n)

Type of Anesthesia Used

General 100.0% (50/50)

Spinal 0.0% (0/50)

Regional 0.0% (0/50)

Local 0.0% (0/50)

Systemic Heparinization 80.0% (40/50)

Spinal CSF Drainage Used 4.0% (2/50)

Any Other Spinal Protective Measure Used 6.0% (3/50)

LSA Coverage

None 42.0% (21/50)

Partial 18.0% (9/50)

Complete 40.0% (20/50)

Subjects with LSA Coverage 58.0% (29/50)

LSA Covered subjects with pre-implant adjunctive procedure1 2.0% (1/50)

Procedures involving LSA bypass/LSA revascularization/LSA debranching/LSA transposition. m = number of subjects in category, n = number of subjects enrolled in this study. Site Reported Table.

A summary of the acute measures at implant are summarized in Figure 48 through Figure 49.

Figure 48. Implant Procedure

40 Instructions for Use English

Duration of Implant Procedure (min)

n 50

Mean ± SD 102.2 ± 57.0

Median 90.5

Min, Max 35, 311

Contrast Volume (ml)

n 471

Mean ± SD 120.8 ± 49.1

Median 110.0

Min, Max 31, 230

Total Fluoroscopic Time (mins)

n 441

Mean ± SD 11.0 ± 10.1

Median 8.7

Min, Max 3, 66

Blood Loss During Procedure (ml)

n 49

1,2

Mean ± SD 123.4 ± 152.9

Median 50.0

Min, Max 10, 900

Subjects Requiring Blood Transfusion % (m/n)3 18.0% (9/50)

Hospital Survival % (m/n) 94.0% (47/50)

Overall Hospital Stay (days)

n 491

Mean ± SD 14.7 ± 12.6

Median 11.0

Min, Max 1, 58

Time in Intensive Care Unit From Admission to Discharge (hours)

n 494

Mean ± SD 201.7 ± 194.3

Median 140.8

Min, Max 3, 976

Most of the subjects were treated emergently in the middle of the night; measurements like contrast

volume, total fluoroscopic time, etc. may not be captured in the research coordinator's absence.

Subject's blood loss information was not reported by the site but was reported that no blood transfusion

was required.

Not limited to blood transfusion required as a result of blood loss during the procedure.

Subject was not discharged at the time of data snapshot date. m = number of subjects in category, n = number of subjects with available data. Site Reported Table.

Primary Endpoint

% (m/n)

30-day All-Cause Mortality 8.0% (4/50)

m = number of subjects in category, n = number of subjects enrolled in this study. Site and clinical events committee (CEC) Adjudicated Reported Table.

6.2.6. Safety and Effectiveness Results

6.2.6.1. Safety Results: Primary and Secondary Endpoint Analysis

The primary endpoint for this study included all enrolled subjects and was measured by the all-cause mortality rate within 30 days. As shown in Figure 50, four (4) subjects died within 30 days of the index procedure. This result demonstrates a 30-day all-cause mortality rate of 8.0% for BTAI subjects treated with the Valiant thoracic stent graft. Two of these deaths were adjudicated by the CEC to be aortic-related resulting in an aortic-related mortality of 4.0% (2/50). Neither of these deaths was reported by the sites to be aortic related (Figure 51).

Figure 49. Acute Measurement at Implant

Figure 50. Primary Endpoint

Instructions for Use English 41

Subject ID

Procedure

Date

Death Date

Time to Death

(days)

Cause of Death

Site Reported

Death

Relatedness

Site Reported

Death

Relatedness CEC

Adjudicated

00018-001 01/25/2011 01/26/2011 1 Hemothorax Not Related Aortic Related1

00182-001 10/06/2010 10/07/2010 1

Traumatic Brain Injury

Not Related Not Related

00344-003 01/26/2011 01/31/2011 5 Arrhythmia Not Related Not Related

00059-002 08/26/2011 09/17/2011 22

Complications of Multiple Blunt Force Injuries

Device Relation

Not Evaluable, Aortic Relation Not Evaluable,

Not Related

to Procedure

Device Related,

Procedure Related,

Aortic Related2

00340-004 04/10/2011 09/26/2011 169 Infection Not Related Not Related

Site and CEC Adjudicated Reported Table.

A 22 year-old male, thrown from a horse into a tree, arrived with bilateral hemothoraces and a myocardial contusion (ISS=30, Grade III aortic injury). The patient underwent prompt and successful thoracic endovascular aneurysm repair (TEVAR), with the post-procedural aortogram demonstrating successful exclusion of BTAI and no extravasation or endoleak. While the left sided hemothorax subsided after TEVAR, the patient expired on the next day from continued right-sided massive hemothorax. An autopsy was performed on this patient and showed no evidence of an additional aortic injury. The CEC adjudicated this death to be related to the aortic injury and unrelated to the device or procedure.

Sudden unexplained death day 22 in acute care facility, with limited information and no autopsy. Subject had a history of atrial fibrillation and recent pulmonary embolus on Coumadin. Imaging taken one week before death showed complete exclusion of pseudoaneurysm and good graft position. Due to unknown cause of death the CEC conservatively adjudicated the event to be related to the device, procedure, and aorta.

Figure 51. Deaths

6.2.6.2. Safety Results: Summary of All Adverse Events (AE)

As stated in the protocol, only those adverse/serious adverse events that are related to the device, to the implant procedure and/or to the aorta and serious adverse events (SAEs) that lead to death, regardless if they are related to the device, procedure or the aorta, were reported by the sites. SAEs are defined as any adverse event that:

led to a death;

•

led to a serious deterioration in the health of the subject that:

•

resulted in life threatening illness or injury;

•

resulted in a permanent impairment of a body structure or a body function;

•

required in-patient hospitalization or prolongation of existing hospitalization; or

•

resulted in medical or surgical intervention to prevent permanent impairment to a body structure or a body function; or

•

led to fetal distress, fetal death or a congenital abnormality or birth defect.

•

The AEs reported during this study are identified in Figure 52. Of note is that no subject had a stroke/cerebrovascular accident, spinal cord ischemia, paraparesis or paraplegia. Adverse events that occurred within 30-days of the procedure and were related to the procedure, aorta or device were reported by the study sites in six (6) subjects (12.0%). Of these

adverse events, procedure related adverse events were reported in five (5) subjects (10.0%), and an aorta related adverse event was reported in one (1) subject (2.0%). The CEC, that adjudicated events associated with deaths, adjudicated one additional SAE as being related to the aorta. There were no adverse events reported to be related to the device by the sites, however the CEC adjudicated one death from unknown causes as related to the procedure, device and aorta, as described above. A listing of all AEs, including those SAEs that led to death, whether or not they were related to the device, procedure or the aorta, is shown in Figure 52.

42 Instructions for Use English

Adverse Event

Relatedness

Site Reported

Relatedness

CEC Adjudicated

Any Procedure, Aorta or

Device Related AE

12.0% (6/50)

N/A

Any Procedure Related AE 10.0% (5/50) N/A

Any Aorta Related AE 2.0% (1/50) N/A

Any Device Related AE 0% (0/50) N/A

SAEs Leading to Death

Hemothorax Not Related Aortic Related

Traumatic Brain Injury Not Related Not Related

Arrhythmia Not Related Not Related

Complications of Multiple

Blunt Force Injuries

Not Evaluable Device

Related,

Not Evaluable Aortic

Related,

Not Related to

Procedure

Device Related,

Aortic Related

SAEs Not Leading to Death

Femoral Artery Dissection

Procedure Related

N/A

Anoxic Encephalopathy

Aortic Related

N/A

Left Arm Ischemia

4,5

Procedure Related

N/A

Left Arm Claudication

Procedure Related

N/A

Additional AEs

Hematoma7 Procedure Related N/A

Incision Site Erythema

Procedure Related N/A

Information on patients who died and had SAEs is provided in Figure 51. These are the only events

adjudicated by the CEC, as the CEC is only responsible for adjudicating deaths and UADE’s.

Subject had a right common femoral artery focal dissection during index procedure. Subject underwent a

thrombectomy and patch angioplasty and the event recovered the same day.

Subject developed an anoxic brain injury related to the rupture on the day of the procedure. This subject’s discharge summary notes mentioned that “the patient’s course was complicated by hypoxicischemic encephalopathy secondary to significant hypotension and hypoxia after the accident as well as intra-operatively” prior to the deployment of the stent graft. Additionally this subject experienced another SAE: infection, on day 169 post procedure that led to death (refer to Figure 51).

Subject had peripheral ischemia on day seven (7), LSA was intentionally (partially) covered during initial procedure. Subject underwent a left carotid to subclavian bypass on day eight (8) and the ischemia resolved the next day.

Subject experienced upper left limb ischemia on day 36 post procedure, related to the procedure. During the procedure, the physician intentionally completely covered the left subclavian artery (LSA). The subject eventually developed signs of upper left extremity ischemia. This subject underwent a left carotid to subclavian bypass on day 36 post procedure that led to resolution of the event on the day of the bypass.

Subject experienced left arm claudication on day 30, LSA was intentionally (completely) covered during initial procedure. Subject underwent left carotid to subclavian bypass on day 103 and the event has since resolved.

Subject developed a right groin hematoma on the day of the index procedure. The event resolved without treatment four (4) days post procedure.

Subject developed erythema at right groin incision on day four (4) from the index procedure. The site reported this event to be related to the procedure. This event resolved the following day with medication.

Procedure Related,

In addition to the events listed above, there was one subject that experienced peripheral arm ischemia on day 36 post-procedure. That same day a left carotid-to-subclavian bypass procedure was performed and the peripheral arm ischemia was resolved on the day of the procedure. The site reported this as procedure related. There was also one subject that experienced no palpable radial pulse on day 39 post-procedure. The site reported this event to be related to the procedure and was 'unresolved, not treating' as of the data cut-off date for the data presented. There was also one death reported after 30-days as described in Figure 51. There were no additional adverse events reported during this study.

6.2.7. Effectiveness Results

To assess the effectiveness of the Valiant thoracic stent graft, the RESCUE trial collected information on the success of device delivery and deployment. Information was also collected on technical observations including endoleaks, stent graft kinking, stent graft twisting, misaligned deployment, stent graft fracture, loss of stent graft integrity, loss of stent graft patency, migration and if the traumatic injury was covered by the stent. In addition, the following device assessments were collected by the sites and verified by the independent core laboratory:

Loss of stent graft patency

•

Total length of the stented segment

•

Stent graft migration

•

Presence and type of endoleaks

•

Figure 52. All Adverse Events Within 30 Days

Instructions for Use English 43

As shown in Figure 53, after gaining vessel access at procedure, the investigators reported that the device was delivered and deployed successfully in all 50 subjects. Delivery and

Secondary Efficacy Endpoint % (m/n)

Successful Delivery and Deployment of the Stent Graft 100.0% (50/50)

m = number of subjects in category, n = number of subjects enrolled in this study. Site and CEC Adjudicated Reported Table.

Secondary Procedure

0 to 30 Days

% (m/n)

31 to 365 Days

% (m/n)

366 to 731 Days

% (m/n)

732 to 1096 Days

% (m/n)

1097 to 1461

Days

% (m/n)

1462 to 1826

Days

% (m/n)

Conversion to Open Repair 0.0% (0/50) 0.0% (0/43) 0.0% (0/11) N/A N/A N/A

Additional Endovascular Device Placed

0.0% (0/50) 0.0% (0/43) 0.0% (0/11) N/A N/A N/A

Other2 2.0% (1/50) 4.7% (2/43) 0.0% (0/11) N/A N/A N/A

m = number of subjects in category, n = number of subjects with study stent implanted who experienced an event or who were followed at least until the lower endpoint of the interval. For example, for column '0-30 Days', '31-365 Days', '366-731 Days', '732-1096 Days', '1097-1461 Days' and '1462-1826 Days', a subject had to be followed respectively for at least 0 day, 31 days, 366 days, 732 days, 1097 days and 1462 days in order to be included in the denominator, unless he/she experienced an event in the corresponding interval. Site Reported Table.

One subject had peripheral ischemia on day seven, LSA was intentionally (partially) covered during initial procedure. Subject underwent a left carotid to subclavian bypass on day eight and the ischemia resolved the next day. Another subject experienced left arm claudication on day 30, LSA was intentionally (completely) covered during initial procedure. Subject underwent left carotid to subclavian bypass on day 103 and the event has since resolved. A third subject experienced peripheral arm ischemia on day 36. On that same day a left carotid-to-subclavian bypass procedure was performed and the peripheral arm ischemia was resolved on the day of the procedure.

deployment was documented by investigators as either successful or not successful on the case report forms. There were no Type I or Type III endoleaks reported in this study population. There were two (2) subjects reported to have a Type II endoleak at the end of procedure by the site, both of these endoleaks resolved without treatment by the 1-month visit. No technical observations were reported from the 1-month follow-up CTA/MRA images. The stent graft integrity was maintained in 100% of the cases. There were no reports of stent graft twisting, kinking, or fracture, and all stent grafts remained patent as reported by the sites and the core lab. There were no occurrences of Unanticipated Adverse Device Effects (UADEs) in this trial.

Figure 53. Secondary Efficacy Endpoint

There were no cases of endovascular re-intervention or conversion to open surgery reported. There was one (1) subject within 30-days and two (2) subjects between 31 and 365 days that required LSA bypass to correct left arm ischemia. These events are captured under the ‘Other’ category in Figure 54 below.

Figure 54. Secondary Procedures (Implanted)

6.2.8. Overall Conclusions

Based on the data collected and presented, there is reasonable assurance of safety and effectiveness of the Valiant thoracic stent graft in the treatment of BTAI of the DTA for subjects who have appropriate vascular anatomy and who are candidates for endovascular treatment.

6.3. VALOR II

6.3.1. VALOR II IDE

The VALOR II IDE clinical study (Valiant Test Group) was a prospective, multicenter, single-arm trial. A total of 160 subjects were enrolled at 24 investigational sites across the United States between December 2006 and September 2009. Adult male and female patients who were considered candidates for elective surgical repair by modified SVS 0, 1, or 2 to repair the DTA, and who met the anatomical criteria for the Valiant device were enrolled in the VALOR II IDE clinical study. Patients were also required to meet inclusion/exclusion criteria before being enrolled.

For the IDE component of the study, the Valiant Test Group was compared on the primary safety endpoint to the Talent Control Group, which was formed by 195 subjects enrolled in a study of the safety and effectiveness of the Talent thoracic stent graft (PMA number P070007)1. Although conducted over different periods of time, the Valiant Test and Talent Control Groups evaluated the same treatment indications and were conducted under similar study requirements. The design of both trials included use of a physician screening committee and a core laboratory and clinical events committee (CEC) to reduce potential selection and assessment bias, respectively. In addition, statistical testing was employed to control differences in baseline risk factors. Nonetheless, there were several potential concerns associated with using a historical control. The control was non-concurrent, so there was a temporal bias of unknown size that may or may not affect the scientific validity of the study. There is no guarantee that the two groups were equivalent, even with statistical techniques such as ANOVA or Cochran-Mantel-Haenszel analysis. In addition to the above concerns, protocol deviations occurred during this study and may have also introduced bias to the data.

The analyses of the IDE study data included endpoints that were consistent with those in current literature and other thoracic endovascular aneurysm repair studies. Hypothesis testing included a comparison of all-cause mortality within 12 months between the Valiant Test Group and Talent Control Group as the primary safety endpoint (Section 6.3.10). The primary effectiveness endpoint (Section 6.3.12), Successful Aneurysm Treatment, which was compared to a fixed value, was defined as the absence of: a) aneurysm growth of more than 5 mm at the 12-month visit relative to the 1-month visit; and b) secondary procedure due to type I or III endoleak performed or recommended at or before the 12-month visit. Secondary endpoints (Section 6.3.11 and Section 6.3.13) were also analyzed. Follow-up evaluations were conducted at 1 month, 6 months, and 12 months. Data collected in electronic case report forms via remote data capture were used for the study analyses. Clinical investigators fully reviewed the data. All deaths and MAEs were adjudicated by an independent clinical events committee (CEC) to determine aneurysm, device, and procedure relatedness.

6.3.2. VALOR II Postapproval Study

As a condition of approval, Medtronic Vascular conducted a postapproval study to evaluate the longer-term safety and effectiveness of the Valiant thoracic stent graft in the treatment of descending thoracic aneurysms (DTA) of degenerative etiology in subjects who are candidates for endovascular repair. This postapproval study consisted of the entire VALOR II IDE cohort, and no additional de novo subjects were required. The subjects enrolled in the VALOR II IDE clinical study were to be followed annually, up to 5 years postimplant, assessing freedom from aneurysm-related mortality (ARM), among other endpoints. ARM is defined as death from rupture of the fusiform aneurysm or saccular aneurysm/penetrating ulcer or from any procedure intended to treat the fusiform aneurysm or saccular aneurysm/penetrating ulcer. If a death occurred within 30 days of any procedure intended to treat the fusiform aneurysm or saccular aneurysm/penetrating ulcer, it is presumed to be aneurysm-related. All deaths were adjudicated by the CEC to determine aneurysm, device, and procedure relatedness.

The primary endpoint of the postapproval component of the VALOR II study was the evaluation of the ARM-free rate in subjects implanted with the Valiant thoracic stent graft 5 years after implantation, comparing it to a predefined performance goal (PG) of 83.4%, which was based on the 5-year ARM rates from the VALOR clinical study (Talent TAA stent graft study) and data from a review of the TEVAR literature. The comparison was based on a Kaplan-Meier (KM) analysis of ARM. The statistical hypothesis was tested by calculating a 1sided 95% confidence limit for the 5-year KM estimate of Valiant thoracic stent graft system subjects. Refer to Section 6.3.11.

Additionally, the following secondary endpoints, which were evaluated at 1 month, 6 months and 12 months for the IDE, continued to be evaluated yearly for 5 years from initial implant.

All-cause mortality (Section 6.3.10)

•

Aneurysm-related mortality (Section 6.3.11)

•

Aneurysm rupture (Section 6.3.11)

•

The summary of Safety and Effectiveness Data and labeling is available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/pma/pma.cfm?num=p070007

44 Instructions for Use English

Conversions to open surgical repair (Section 6.3.11)

•

One or more major adverse events (Section 6.3.11)

•

Secondary endovascular procedures (Section 6.3.12)

•

Aneurysm enlargement (Section 6.3.12)

•

Endoleaks (Section 6.3.13)

•

Stent graft migration (Section 6.3.13)

•

Loss of stent graft patency (Section 6.3.13)

•

Device integrity (Section 6.3.13)

•

The VALOR II postapproval study was completed in October 2014. Of the 160 subjects enrolled in the IDE cohort, 93 subjects completed the postapproval study. Figure 55 contains a summary of subject accountability. Visit Compliance Rates, shows that approximately 80% of the visits throughout the study took place within visit windows.

Figure 55. VALOR II Subject Accountability

6.3.3. Data collected Preapproval and Postapproval

One year IDE data was used to obtain PMA approval for Valiant thoracic stent graft with the Captivia delivery system. As explained in Section 6.3.2, Medtronic Vascular conducted a postapproval study, as a condition of approval, to evaluate the longer-term safety and effectiveness of the Valiant thoracic stent graft in the treatment of DTA. As part of this postapproval study, the IDE subjects were followed to 5 years. No de novo subjects were enrolled. The VALOR II endpoint findings, including the data from the postapproval study, are captured in Section 6.3.10 through Section 6.3.13

6.3.4. Subject Accountability and Follow Up through 5 years

Figure 56 contains subject accountability and imaging compliance data. This is based on monitored data from case report forms entered by clinical sites into the electronic data capture (EDC) system. As shown in Figure 56, 93 subjects completed the study.

Instructions for Use English 45

Patient follow-up

# (%)

Patients with Imaging

(at each time interval)

# (%)

Patients with adequate imaging to assess

the parameter

# (%)

Patient events

Treatment /

Follow-up

Interval

Eligible

Treatment

or clinical

f/u

Imaging

f/u

CT/MR

imaging

Chest

X-Ray

Additional

imaging

modalities

Max ANR

diameter

Change in

ANR

diameter

(from 1-

month)

Endo-

leak

Migration

(from 1-

month)

Integrity

Intent to treat

but not implanted

Conversion

to surgery

Death Withdrawal

LTF

Implant

160

(100.0%)

Events between

implant and pre-

discharge

Pre-discharge

157

(100.0%)

(42.7%)

(15.9%)

(37.6%)

(0.0%)

(15.9%)

(15.3%)

(37.6%)

Events between pre-

discharge and 1-

month follow-up visit

140

(92.1%)

147

(96.7%)

143

(94.1%)

133

(87.5%)

(0.0%)

143

(94.1%)

136

(89.5%)

133

(87.5%)

Events between 1-

and 6-month follow-

up visits

112

(75.7%)

115

(77.7%)

111

(75.0%)

(65.5%)

(0.0%)

111

(75.0%)

108

(73.0%)

101

(68.2%)

114

(77.0%)

(66.2%)

Events between 6-

and 12-month follow-

up visit

109

(78.4%)

114

(82.0%)

112

(80.6%)

105

(75.5%)

(0.0%)

112

(80.6%)

105

(75.5%)

(69.8%)

114

(82.0%)

105

(75.5%)

Events between 12-

month and 2-year

follow-up visit

(61.6%)

Events between 2-

and 3-year follow-up

visit

(71.8%)

(76.9%)

(71.8%)

(70.9%)

(0.0%)

(70.9%)

(67.5%)

(59.8%)

(76.9%)

(70.9%)

Events between 3-

and 4-year follow-up

visit

(68.0%)

(71.8%)

(68.9%)

(60.2%)

(68.0%)

(64.1%)

(59.2%)

(71.8%)

(60.2%)

Events post 4-year

follow-up visit

Results for the following categories have a hierarchical relationship in this order: intent to treat but not implanted, conversion to surgery, death, withdrawal, lost to follow‐up (LTF). A hierarchical

structure facilitates tracking of eligibility, imaging, and follow-up.

“Events between implant and pre-discharge” includes events that took place at implant. Similarly, “Events between 1-month and 6-months follow-up” includes events that occurred at the

1‐month follow-up visit. The same principle applies to subsequent intervals.

(72.8%)

(76.0%)

(70.4%)

(61.6%)

(0.0%)

(69.6%)

(64.8%)

(62.4%)

(72.8%)

541

0 0

0000

0 9

0 8

Total 3

(65.6%)

(74.2%)

(63.4%)

(60.2%)

(72.0%)

(0.0%)

(65.6%)

(72.0%)

(74.2%)

(73.1%)

103

117

125

139

148

152

157

160

5-year

4-year

3-year

2-year

12-month

6-month

1-month

6.3.5. Study Demographics and Baseline Medical History

There were no statistically significant differences in demographic variables between Valiant Test Group and Talent Control Group populations. Figure 57 through Figure 60 provide the demographics, baseline medical history, and SVS risk classification of both groups.

Figure 56. Subject Accountability and Imaging Compliance through 5 Years

46 Instructions for Use English

VALIANT TEST

GROUP

TALENT

CONTROL

GROUP

p-value

Age (years)

Total Population

591061N

0.45970.2 ± 11.172.2 ± 9.1Mean ± SD

7374Median

27, 8636, 85Min, max

Sex/Gender % (m/n)

)591/511(%95)061/59(%4.95Male

)591/08(%14)061/56(%6.04Female

0.769

Race % (m/n)

American Indian or Alaska Native 0% (0/160) 0% (0/190)

Asian/Native Hawaiian/Pacific Islander 2.5% (4/160) 1.1% (2/190)

)091/52( %2.31 )061/61( %01Black

)091/261( %3.58 )061/831( %3.68White

)091/0( %0 )061/0( %0Subject refuses to answer

0.787

)091/1( %5.0 )061/2( %3.1Multi-racial / other

Figure 57. Subject Demographics

Medical History

VALIANT TEST

GROUP % (m/n)

(N = 160)

TALENT

CONTROL GROUP

% (m/n)

(N = 195) p-value

Cardiovascular

Abdominal aortic aneurysm (AAA) 38.8% (62/160) 19% (37/195) <0.001

100.0< )591/4( %1.2 )061/33( %6.02 riaper AAA suoiverP

Ascending thoracic aneurysm

8.1% (13/160)

490.0 )591/82( %4.41 )061/51( %4.9 anignA

206.0 )591/25( %7.62 )061/05( %3.13 aimhtyhrrA

100.0< )591/11( %6.5 )061/54( %1.82 esaesid yretra ditoraC

645.0 )591/71( %7.8 )061/91( %9.11 eruliaf traeh evitsegnoC

829.0 )591/97( %5.04 )061/17( %4.44 esaesid yretra yranoroC

664.0 )591/02( %3.01 )061/22( %8.31 gnitfarg ssapyb yretra yranoroC

681.0 )591/071( %2.78 )061/051( %8.39 noisnetrepyH

711.0 )591/72( %8.31 )061/43( %3.12 noitcrafni laidracoyM

Percutaneous coronary intervention 16.9% (27/160) 5.6% (11/195) 0.002

190.0 )591/23( %4.61 )061/04( %52 esaesid ralucsav larehpireP

Pulmonary

Chronic obstructive pulmonary disorder 35% (56/160) 36.9% (72/195) 0.426

Renal

974.0 )591/43( %4.71 )061/62( %3.61 ycneiciffusni laneR

Cerebrovascular / Neurological

174.0 )591/51( %7.7 )061/81( %3.11 kcatta cimehcsi tneisnarT

859.0 )591/91( %7.9 )061/71( %6.01 tnedicca ralucsav larbereC

883.0 )591/2( %1 )061/0( %0 aigelparaP

489.0 )591/1( %5.0 )061/1( %6.0 siseraparaP

Other Abnormal Body Systems

499.0 )591/5( %6.2 )061/4( %5.2 redrosid gnideelB

624.0 )591/13( %9.51 )061/43( %3.12 setebaiD

600.0 )591/501( %8.35 )061/56( %6.04 snoitacilpmoc lanitsetniortsaG

100.0< )591/58( %6.34 )061/811( %8.37 aimedipilrepyH

Tobacco use in last ten years

44.4% (71/160) 50.3% (98/195) 0.333

Data point was not collected in Talent Control Group.

For Talent Control Group, subjects who answered ‘Yes’ to ‘Tobacco Use’ and whose resolution date was more than 10

years prior to implant were considered as ‘No’ to the question of ‘Tobacco Use in the last 10 years’.

Etiology

VALIANT TEST GROUP

% (m/n)

(N = 160)

TALENT CONTROL GROUP

% (m/n)

(N = 195)

Thoracic Aortic Aneurysm (Fusiform)

64.4% (103/160) 57.4% (112/195)

Thoracic Aortic Aneurysm (Saccular/Penetrating ulcer)

)591/07( %9.53 )061/75( %6.53

)591/31( %7.6 )061/0( %0 Both

There were several differences in baseline medical risk factors between the Valiant Test Group and Talent Control Group. Significant differences were found in a history of abdominal aortic aneurysm (AAA), prior AAA repair, carotid artery disease, angina, percutaneous coronary intervention, and hyperlipidemia. Additionally, the history of ascending thoracic aneurysms and the use of an abdominal aortic conduit for vascular access, both of which were exclusion criteria in the Talent Control Group, likely added to an increase in baseline risk factors for the Valiant Test Group.

Figure 58. Baseline Medical History

More subjects in the Valiant Test Group had higher SVS scores as compared to Talent Control Group subjects.

Figure 59. Anatomic Lesion Type

Instructions for Use English 47

SVS/AAVS Score1

VALIANT TEST GROUP

% (m/n)

(N = 160)

TALENT CONTROL

GROUP % (m/n)

(N = 195) p-value

)591/8( %1.4 )061/1( %6.0 0

)591/14( %12 )061/71( %6.01 1

)591/241( %8.27 )061/041( %5.78 2

)591/4( %1.2 )061/2( %3.1 3

0.002

Modified SVS/AAVS Medical Comorbidity Grading System modified for age, hypertension, cardiac, pulmonary, and

renal.

p-value is calculated using one-way ANOVA with SVS score being the dependent variable.

Figure 60. Baseline Modified SVS/AAVS Classification

Baseline Vessel Dimension

VALIANT TEST

GROUP

(N = 160)

TALENT CONTROL

GROUP

(N = 195) P-value

Proximal Neck Diameter (mm)

781 751

470.0 39.4±02.13 71.5±74.23 DS ± naeM

05.13 23 naideM

5.34 ,5.81 5.15 ,12 xaM ,niM

Max Aneurysm Diameter (mm)

781 061

363.0 06.11±15.55 30.11±75 DS ± naeM

65 1.65 naideM

8.88 ,2.62 7.79 ,4.13 xaM ,niM

Distal Neck Diameter (mm)

481 751

050.0 5±27.92 87.5±32.13 DS ± naeM

5.92 5.03 naideM

5.24 ,71 15 ,91 xaM ,niM

Proximal Centerline Neck Length (mm)

781 751

288.0 90.25±20.08 50.15±30.38 DS ± naeM

9.77 08 naideM

432 ,01 5.642 ,41 xaM ,niM

Aneurysm Length (mm)

081 451

168.0 96.27±83.121 20.37±52.321 DS ± naeM

56.701 55.801 naideM

5.792 ,8 0.613 ,71 xaM ,niM

Distal Neck Length (mm)

481 851

117.0 9.26±09 25.85±26.09 DS ± naeM

5.37 50.97 naideM

552 ,9 582 ,0 xaM ,niM

Right External Iliac Minimum Diameter (mm)

221 021

110.0 35.1±94.6 69.1±70.7 DS ± naeM

5.6 7 naideM

11 ,9.2 5.31 ,5.3 xaM ,niM

Left External Iliac Minimum Diameter (mm)

421 021

640.0 55.1±95.6 39.1±40.7 DS ± naeM

5.6 7 naideM

9.01 ,3.3 31 ,5.3 xaM ,niM

Each variable will be assessed for balance between the treatment groups. This assessment is also adjusted for SVS

score of (0, 1) versus (2, 3).

n = number of known values.

6.3.6. Baseline Aneurysm Data

Figure 61 and Figure 62 provide the baseline aneurysm and anatomical measurements of the Valiant Test Group and the Talent Control Group study populations.

Figure 61. Baseline Vessel Dimensions - Core Laboratory Reported

48 Instructions for Use English

Diameter (mm)

VALIANT TEST GROUP

% (m/n)

TALENT CONTROL GROUP

% (m/n)1

)781/0( %0 )061/0( %0 71-01

)781/1( %5.0 )061/0( %0 92-81

)781/41( %5.7 )061/7( %4.4 93-03

)781/83( %3.02 )061/52( %6.51 94-04

)781/56( %8.43 )061/27( %54 95-05

)781/64( %6.42 )061/93( %4.42 96-06

)781/91( %2.01 )061/21( %5.7 97-07

)781/4( %1.2 )061/2( %3.1 98-08

)781/0( %0 )061/3( %9.1 99-09

)781/0( %0 )061/0( %0 901-001

)781/0( %0 )061/0( %0 911-011

)781/0( %0 )061/0( %0 +021

Aneurysm diameter

<50 mm (%m/n)

)781/35( %3.82 )061/23( %02

Aneurysm diameter

>50 mm (% m/n)

)781/431( %7.17 )061/821( %08

m = numbers in category, n = number of known values.

Figure 62. Baseline Maximum Aneurysm Diameters – Core Laboratory Reported

Number of Devices Implanted

VALIANT TEST GROUP

% (m/n)

N = 160

TALENT CONTROL GROUP

% (m/n)

N = 195

)591/1( %5.0 )061/3( %9.1

)591/83( %5.91 )061/26( %8.83 1 )591/65( %7.82 )061/46( %04 2 )591/84( %6.42 )061/62( %3.61 3 )591/43( %4.71 )061/5( %1.3 4

)591/41( %2.7 )061/0( %0 5 )591/3( %5.1 )061/0( %0 6 )591/1( %5.0 )061/0( %0 +7

N is the number of enrolled subjects.

Three enrolled subjects did not receive a stent graft due to a failure to achieve access.

Proximal Diameter

Number of Devices

% (m/n)1

)882/1( %3.0 42

)882/2( %7.0 62

)882/4( %4.1 82

)882/6( %1.2 03

)882/33( %5.11 23

)882/42( %3.8 43

)882/04( %9.31 63

)882/53( %2.21 83

)882/84( %7.61 04

)882/62( %9 24

)882/33( %5.11 44

)882/63( %5.21 64

1 m is the number of devices of that proximal diameter implanted and n is the total number of devices implanted.

6.3.7. Devices Implanted

A total of 288 stent grafts and an average of 1.8 stent grafts per subject were implanted in the Valiant Test Group. Figure 63 to Figure 65 provide a breakdown of the number of devices implanted in both the Valiant Test Group and the Talent Control Group.

Figure 63. Number of Devices Implanted

Sizes of Devices Implanted

Figure 64. Devices Implanted by Proximal Diameter

Figure 65 tabulates the various configurations of the Valiant thoracic stent grafts implanted per subject for the Valiant Test Group. One subject was implanted with a distal device in the proximal position which was a deviation from the protocol.

Instructions for Use English 49

)1n/m( % noitarugifnoC eciveD

)2751/651( %4.99 thgiartS olFeerF lamixorP

)751/64( %3.92 thgiartS beW desolC latsiD

)751/83( %2.42 Tapered beW desolC latsiD

)751/8( %1.5 thgiartS gnirpS eraB latsiD

m = numbers in subjects who are implanted with the corresponding device, n = total number of implanted subjects.

One subject was implanted with a Closed Web device in the proximal position due to an adjustment in size made at the

time of procedure.

6.3.8. Acute Procedural Data

Procedure Details % (m/n)1

Left Subclavian Artery (LSA) Revascularization Pre-Implant or at Initial Procedure

13.8% (22/160)

)061/2( %3.1 noitisopsnart naivalcbus tfeL

)061/02( %5.21 ssapyb naivalcbus ot ditoraC

Arterial Access2

)061/3( %9.1 tiudnoc citroa lanimodbA

Iliac conduit 13.1% (21/160)

Femoral/Iliac artery 85.6% (137/160)

Anesthesia2

General 88.1% (141/160)

Epidural 0% (0/160)

Spinal 8.1% (13/160)

Local 5.6% (9/160)

Spinal Protection

Spinal CSF drainage 53.8% (86/160)

Implantation Zone of Proximal Component

Zone 0 0% (0/157)

Zone 1 0% (0/157)

Zone 2 31.2% (53/157)

Zone 3 46.5% (73/157)

Zone 4 22.3% (35/157)

LSA Coverage

Complete 27.4% (43/157)

Partial 5.1% (8/157)

None 67.5% (106/157)

m = numbers in category, n = number of known values.

Not mutually exclusive.

Parameter

VALIANT TEST

GROUP

VALIANT TEST

GROUP

TALENT CONTROL

GROUP

TALENT CONTROL

GROUP

Subjects requiring transfusion %

(m/n)

160 10% (16/160) 194 22.7% (44/194)

Blood loss during procedure (cc) Mean±SD

153 277±468.8 189 371.2±514.4

Duration of procedure (min) Mean±SD 160 119.7±54.8 194 154.2±76

Time in ICU (hours) Mean±SD 160 66.5±112.3 193 46.8±114.3

Overall hospital stay (days) Mean±SD 160 6.1±8.9 195 6.4±11.5

m = numbers in category, n = number of known values.

Implant procedure data are presented in Figure 66.

Figure 65. Type of Devices Implanted - Valiant Test Group only

6.3.9. Clinical Utility Data

Figure 67 presents the clinical utility measures in the Valiant Test Group and the Talent Control Group.

Figure 66. Acute Procedural Details : Valiant Test Group

6.3.10. Primary Safety Endpoints

The primary safety endpoint for the VALOR II IDE study was all-cause mortality evaluated through 12 months. The rate of all-cause mortality within 12 months in the Valiant Test Group was 12.6% (19/151) which compared to 16.1% (31/192) observed in the Talent Control Group. As shown in Figure 68, the upper endpoint of 1.18 of the adjusted odds ratio between the groups was below a predetermined noninferiority margin of 2.25, thereby demonstrating the primary safety objective. All enrolled subjects were included in the analysis,

50 Instructions for Use English

Figure 67. Clinical Utility Data

including 3 subjects who were not implanted due to a failure to achieve vessel access. A subject was considered officially enrolled when an access site incision was made. This group

IDE Primary Safety Endpoint: All-Cause Mortality at 12-Months

% (m/n)

(upper endpoint of

1-sided 95% CI)

Odds Ratio

(upper endpoint of

1-sided 95% CI)2

p-value for

nonhomogeneity

)%9.71( )151/91( %6.21 puorG tseT tnailaV

)%2.12( )291/13( %1.61 puorG lortnoC tnelaT

0.70 (1.18) 0.719

The numerator m is the number of ITT subjects who died within 365 days; the denominator n is the number of ITT

subjects followed through at least 337 days. A subject was considered enrolled when an access site incision was made.

The noninferiority test was performed using the Cochran-Mantel-Haenszel (CMH) test to adjust for SVS scores of (0,1) versus (2, 3). The required assumption of homogeneity among the odds ratios defined by the SVS score strata was statistically tested using the Breslow-Day test.

100

0 30 60 90 120 150 180 210 240 270 300 330 360 390

Kaplan-Meier estimate ± standard error at 365 days:

Valiant Test Group: 87.7%±2.7%

Talent Control Group: 83.9%±2.6%

Vertical bars represent 95% confidence interval

puorG lortnoC tnelaT puorG tseT tnailaV

563 ot 481 381 ot 13 03 ot 0 563 ot 481 381 ot 13 03 ot 0 syaD

No. at Risk

160 155 150 195 190 176

No. of Events 5 4 10 4 13 14

No. Censored2 0 1 22 1 1 1

Kaplan-Meier Estimate

96.9% 94.4% 87.7% 97.9% 91.2% 83.9%

(2-sided 95% CI)3 (92.7%,

98.7%)

(89.5%, 97%) (81.3%, 92%) (94.6%,

99.2%)

(86.3%,

94.5%)

(78%, 88.4%)

Standard Error3 1.4% 1.8% 2.7% 1% 2% 2.6%

Number of subjects at risk at the beginning of an interval.

Subjects are censored because the last follow-up has not reached the end of the time interval. Censored subjects will include those who withdraw or are lost to follow-up.

Kaplan-Meier Estimate and Standard Error, and 95% CI were calculated at the end of a time interval.

of subjects is referred to as the intent-to-treat (ITT) population. Five of 19 deaths occurred within 30 days. All 5 deaths were adjudicated as aneurysm-related by the CEC and per the Valiant Test Group clinical study protocol. There were no

aneurysm-related deaths after 30 days and within 365 days.

Figure 68. Primary Safety Endpoint: VALOR II

A Kaplan-Meier analysis of freedom from all-cause mortality was performed and plotted in Figure 69.

Figure 69. Kaplan-Meier Curve of Freedom from All-Cause Mortality within 12 Months

As part of the postapproval study, all-cause mortality for the subjects in the IDE cohort was collected through 5 years, as detailed below.

Figure 70. Kaplan-Meier Estimates of Freedom from All-Cause Mortality within 12 Months

Instructions for Use English 51

All-Cause Mortality through 5 Years

Aneurysm-Related Mortality%

3.8% (6/160)

0.0% (0/160)

30.0% (48/160)

Stent Graft Caused / Contributed to Event

Procedure Caused / Contributed to Event

Device-Related

Not Device-Related

Unknown

Procedure-related

Not Procedure-related

100

0 365

160 135

64.3%

± SE 3.9%

125 116 100

731 1096 1461 1826

Survival Distribution Function (%)

Survival Time In Days

Number of subjects at risk:

Figure 71 summarizes the rates of device-related and procedure-related events among all-cause mortality as adjudicated by the CEC through 5 years. Overall, the CEC determined that 3.8% (6/160) of subjects had device-related deaths and 3.8% (6/160) had procedure-related deaths.

Figure 71. Summary of All-Cause Mortality through 5 Years (CEC Adjudicated)

The Kaplan-Meier analysis in Figure 72 and Figure 73 show that freedom from all-cause mortality within five years is 64.3% with a standard error of 3.9%.

52 Instructions for Use English

Figure 72. Kaplan-Meier Curve of Freedom from All-Cause Mortality at 5 years

Field “Number at Risk” represents subjects at risk of mortality (i.e., alive, not exited) at the beginning of an interval.

Subjects are censored because their last follow-up has not reached the end of the time interval. Censored subjects will include those who

withdraw or are lost to follow-up.

Kaplan-Meier Estimate was calculated at the end of time interval.

Standard Error was calculated at the end of time interval.

100

64.3%

3.9%

1462 to

1826 days

116

69.9%

3.7%

1097 to

1461 days

125

78.2%

3.3%

732 to

1096 days

135

82.8%

3.0%

366 to

731 days

151

87.4%

2.6%

184 to

365 days

155

94.4%

1.8%

31 to

183 days

160

96.9%

1.4%

0 to

30 days

No. at Risk

No. of Events

No. Censored

Kaplan-Meier Estimate

Standard Error

Figure 73. Kaplan-Meier Estimates of Freedom from All-Cause Mortality at 5 Years

Secondary Endpoints

:syad 03 nihtiW

Perioperative mortality

)591/4( %1.2 )061/5( %1.3

Paraplegia

)591/3( %5.1 )061/1( %6.0

Paraparesis

)591/41( %2.7 )061/3( %9.1

One or more Major Adverse Events (MAE)1 38.1% (61/160) 41% (80/195)

:shtnom 21 nihtiW

Aneurysm-related mortality

)291/6( %1.3 )151/5( %3.3

Aneurysm rupture

)291/1( %5.0 )451/0( %0

Conversion to open surgical repair

)291/1( %5.0 )451/0( %0

One or more Major Adverse Events (MAE)1 48.7% (75/154) 53.6% (103/192)

CEC reported

Site reported

Talent Test Group(m/n)

Valiant Test Group(m/n)

6.3.11. Secondary Safety Endpoints

A summary of secondary IDE safety endpoints is presented in Figure 74 and a detailed discussion of each endpoint is provided below.

Figure 74. Summary of IDE Secondary Safety Endpoints

Perioperative Mortality

Five deaths occurred within 30 days in the VALOR II clinical study (3.1%). One subject died due to an aortic rupture at the time of procedure. The rupture occurred during advancement of the stent graft system in a subject with severe tortuosity of the thoracic aorta. One subject died following an acute dissection of the ascending aorta 3 days post procedure. An autopsy revealed a dissection extending from a point 1 to 2 cm proximal to the stent graft to the heart. Three other subjects expired due to pneumonia, respiratory failure, and multisystem organ failure.

Paraplegia and Paraparesis within 30 Days

One subject (1/160, 0.6%) experienced paraplegia 1 day following implant. The subject continued to be active in the trial albeit with permanent adverse sequelae. Three subjects (3/160, 1.9%) experienced paraparesis within 30 days of implant. Two of the 3 subjects continued to be active in the study, one with ongoing paraparesis and the other with paraparesis resolved 5 days post surgery. The third subject died 21 days post-procedure due to respiratory failure and had continuing paraparesis at time of death.

Aneurysm-Related Mortality (ARM) through 1 Year

Five deaths within 365 days in the Valiant Test Group were adjudicated by the CEC to be aneurysm-related (5/151, 3.3%). Each death occurred within the first 30 days and was therefore classified as aneurysm related per protocol. A Kaplan-Meier analysis revealed freedom from ARM within 365 days was 96.9% with a standard error of 1.4%. This analysis is presented in Figure 75.

Instructions for Use English 53

100

0 30 60 90 120 150 180 210 240 270 300 330 360 390

Kaplan-Meier estimate ± standard error at 365 days:

Valiant Test Group: 96.9%±1.4%

Talent Control Group: 96.9%±1.3%

Vertical bars represent 95% confidence interval

Figure 75. Kaplan-Meier Curve of Freedom from Aneurysm-Related Mortality within 12 Months

puorG lortnoC tnelaT puorG tseT tnailaV

563 ot 481 381 ot 13 03 ot 0 563 ot 481 381 ot 13 03 ot 0 syaD

No. at Risk

160 155 150 195 190 176

No. of Events 5 0 0 4 1 1

No. Censored2 0 5 32 1 13 14

Kaplan-Meier Estimate3 96.9% 96.9% 96.9% 97.9% 97.4% 96.8%

(2-sided 95% CI)

98.7%)

(92.7%,

98.7%)

(92.7%,

98.7%)

(94.6%,

99.2%)

(93.9%,

98.9%)

(93.1%,

98.6%)

Standard Error3 1.4% 1.4% 1.4% 1% 1.1% 1.3%

Number of subjects at risk at the beginning of an interval.

Subjects are censored because the last follow-up has not reached the end of the time interval. Censored subjects will

include those who withdraw, are lost to follow-up, or die from causes adjudicated to be unrelated to the aneurysm.

Kaplan-Meier Estimate and Standard Error and 95% CI were calculated at the end of a time interval.

(92.7%,

Figure 76. Kaplan-Meier Estimates of Freedom from Aneurysm-Related Mortality within 12 Months

As part of the postapproval study, data on aneurysm-related mortality (ARM) for the subjects in the IDE cohort was collected through 5 years. A detailed discussion of the results for this endpoint is provided below.

Aneurysm-Related Mortality (ARM) through 5 Years

ARM is defined as death occurring within 30 days from initial implantation or occurring as a consequence of an aneurysm rupture, a conversion to open repair, or any other secondary endovascular procedure related to the aneurysm being treated by the Valiant thoracic stent graft system, as evidenced by CT, angiography, or direct observation at the surgery or autopsy. Additionally, if a death was reported to be related to the procedure or the device, even if it did not take place within 30 days, it was classified as being aneurysm-related. The CEC adjudicated all deaths, determining ARM status (Figure 77). As mentioned in the ARM through 1 year section, 5 deaths took place within 30 days after the index implant and were classified as being related to the aneurysm regardless of cause of death. An independent Clinical Events Committee (CEC) reviewed all deaths throughout the study and classified 3 additional nonperioperative deaths (ie, beyond 30 days of the index implant) as being related to the aneurysm as follows:

1. A subject died 80 days after the procedure due to cardiac standstill secondary to ventricular arrhythmias; the death was adjudicated as being related to the procedure and to the aneurysm.

2. A subject died 163 days after the procedure due to the acute aortic dissection. The dissection started at the proximal end of the stent graft. Death was adjudicated as being related to the device and to the aneurysm.

3. A subject died 1067 days after the procedure due to a thoracic aneurysm rupture. The investigator assigned cause of death to the potential aneurysm rupture caused by Type unknown endoleak (ie, observable endoleak from unknown origin). The CEC adjudicated this death as being related to the aneurysm.

54 Instructions for Use English

Aneurysm-Related Mortality%

3.8% (6/160)

0.0% (0/160)

1.3% (2/160)

Stent Graft Caused / Contributed to Event

Procedure Caused / Contributed to Event

Device-Related

Not Device-Related

Unknown

Procedure-related

Not Procedure-related

Death due to procedural aortic rupture at day zero, and death due to pneumonia at 12 days were classified as being unrelated to the device. However, these deaths were classified as being related to the aneurysm because they took place within 30 days after the index procedure.

Death due multi-organ system failure at 3 days after index procedure, and death due to pneumonia at 12 days were classified as being unrelated to the procedure. However, these deaths were classified as being related to the aneurysm because they took place within 30 days after the index procedure.

Figure 77. Summary of Aneurysm-Related Mortality through 5 Years (CEC Adjudicated)

100

0 365

160 135

94.8%

± SE 1.8%

125 116 100

731

1096 1461 1826

Survival Distribution Function (%)

Survival Time In Days

Number of subjects at risk:

In Figure 78 and Figure 79, the Kaplan-Meier analysis shows that freedom from aneurysm-related mortality within five years is 94.8% with a standard error of 1.8%.

Figure 78. Kaplan-Meier Curve of Freedom from Aneurysm-Related Mortality at 5 years

Instructions for Use English 55

Field “Number at Risk” represents subjects at risk at the beginning of an interval.

Subjects are censored because their last follow-up has not reached the end of the time interval. Censored subjects will include those who

withdraw, are lost to follow-up, or who die from non-aneurysm related causes.

Kaplan-Meier Estimate was calculated at the end of time intervals.

Standard Error was calculated at the end of time intervals.

100

94.8%

1.8%

1462 to

1826 days

116

94.8%

1.8%

1097 to

1461 days

125

94.8%

1.8%

732 to

1096 days

135

95.6%

1.6%

366 to

731 days

151

95.6%

1.6%

184 to

365 days

155

95.6%

1.6%

31 to

183 days

160

96.9%

1.4%

0 to

30 days

No. at Risk

No. of Events

No. Censored

Kaplan-Meier Estimate

Standard Error

Figure 79. Kaplan-Meier Estimates of Freedom from ARM at 5 years

94.8%

[90.9%, 97.1%] 83.4%

Freedom From Aneurysm‐Related Mortality Through 1825 Days

[90% Confidence

Interval]

VALOR-IIPrimary Postapproval Study Endpoint

Based on eight aneurysm-related deaths within 5 year follow-up

)1n/m( % syad 03-0 )2n/m( % syad 563-0

Category

VALIANT TEST

GROUP

TALENT CONTROL

GROUP

VALIANT TEST

GROUP

TALENT CONTROL

GROUP

Mortality 3.1% (5/160) 2.1% (4/195) 12.6% (19/151) 16.1% (31/192)

Respiratory Complications 9.4% (15/160) 13.3% (26/195) 14.9% (23/154) 24% (46/192)

Renal Complications 5% (8/160) 6.2% (12/195) 8.4% (13/154) 10.4% (20/192)

Cardiac Complications 15% (24/160) 12.3% (24/195) 20.1% (31/154) 21.9% (42/192)

Neurological Complications 5% (8/160) 11.8% (23/195) 10.4% (16/154) 16.1% (31/192)

Gastrointestinal Complications 1.3% (2/160) 1% (2/195) 2.6% (4/154) 1.6% (3/192)

Major Bleeding Complications 6.9% (11/160) 15.4% (30/195) 7.8% (12/154) 16.7% (32/192)

Vascular Complications 20.6% (33/160) 21% (41/195) 24% (37/154) 24.5% (47/192)

Any MAE 38.1% (61/160) 41% (80/195) 48.7% (75/154) 53.6% (103/192)

m is the number of subjects experiencing a certain event within 30 days, n is the number of ITT subjects.

m is the number of subjects experiencing a certain event at the interval of 0-365 days, n is the number of subjects who either

experienced at least 1 MAE or secondary procedure in the interval or are followed for at least 337 days.

As shown in Figure 80, the lower 1-sided 95% confidence limit is greater than the performance goal (PG). As a result, the PG was met. Per the study protocol, the null hypothesis was rejected in favor of the alternative hypothesis (H0: ARMF5 ≤83.4%; HA: ARMF5 > 83.4%, where ARMF5 is the Kaplan-Meier estimate of the ARM-free rate at five years, expressed as a percentage).

Figure 80. Postapproval Study Primary Endpoint Analysis

Major Adverse Events through 1 Year

Adverse events in the Valiant Test Group and the Talent Control Group were categorized by severity as Major Adverse Events (MAEs). MAEs were defined as the occurrence of any of the following:

Death:

•

■

due to complications of the procedure, including bleeding, vascular repair, transfusion reaction, or conversion to open surgical TAA repair

■

within the relevant period (30 days or 12 months) of the baseline implant or surgical procedure

Respiratory complications (atelectasis/pneumonia, pulmonary embolism, pulmonary edema, respiratory failure)

•

Renal complications (renal failure, renal insufficiency)

•

Cardiac: MI, unstable angina, new arrhythmia, exacerbation of congestive heart failure (CHF)

•

Neurological: new CVA/embolic events, paraplegia/paraparesis

•

Gastrointestinal: bowel ischemia

•

Major bleeding complication

•

Vascular complications

•

Figure 81 below presents a summary of the CEC reported MAEs through 12 months.

As part of the postapproval study, data on major adverse events (MAE) for the subjects in the IDE cohort was collected through 5 years. A detailed discussion of the results for this endpoint is provided below.

Major Adverse Events (MAEs) 1 Year through 5 Years

The major adverse event (MAE) construct was originally designed to allow for comparison to open surgical repair. Therefore, MAEs are defined as events that are relevant to the surgical treatment of thoracic aortic aneurysms. Figure 81 includes MAEs through 12 months, which were CEC-reported per study protocol. Figure 82 contains MAEs from 1 to 5 years, which were obtained from a composite based on site-reported events. It is possible for a subject to experience multiple or persistent MAEs at more than one time period, so the same subject may appear across multiple timeframes and MAE categories.

56 Instructions for Use English

Figure 81. Summary of MAEs within 12 Months - CEC Reported

Respiratory Complications

Respiratory failure

Pneumonia

Atelectasis

Pulmonary embolism

Pulmonary edema

Renal Complications

Renal insufficiency

Renal failure

Cardiac Complications

Myocardial Infarction

Unstable angina

New arrhythmia / Cardiac arrest

Exacerbation of CHF

Multi-organ Failure

Neurological Complications

Stroke / CVA

Transient Ischemic Attack

Paraplegia / Paraparesis

Gastrointestinal Complications

Bowel ischemia

Major Bleeding Complications

Coagulopathy

Vascular Complications

AV fistula

Hematoma

Vessel (including aorta) rupture/dissection

Embolism (not CVA/TIA/ Pulmonary)

Arterial Occlusion

Retroperitoneal bleed

Thrombosis

Pseudoaneurysm

Vessel Disruption

Aneurysm Rupture

Any MAE

Major bleeding event, procedural or post-procedure

Category

366-731 days

% (m/n)

732-1096 days

% (m/n)

1097-1461 days

% (m/n)

1462-1826 days

% (m/n)

7.5% (10/133) 6.5% (8/124) 8.8% (10/114) 7.1% (7/98)

1.5% (2/133) 2.4% (3/124) 1.8% (2/114) 0.0% (0/98)

0.0% (0/98)

1.5% (2/133)

0.0% (0/124)

0.0% (0/124) 0.9% (1/114) 0.0% (0/98)

0.0% (0/133)

0.8% (1/133)

0.0% (0/133)

Despite being major adverse events, category “All-cause mortality” and sub-category” Aneurysm-related mortality” were NOT included in table, as they were

discussed previously in this document.

m is the number of subjects that experienced a certain event in the interval 366-731 days; n is the number of subjects who experienced at least one MAE in the

interval, underwent a secondary procedure within 731 days, orwere followed for at least 674 days.

m is the number of subjects that experienced a certain event in the interval 732-1096 days; n is the number of subjects who experienced at least one MAE in the

interval, underwent a secondary procedure within 1096 days, or were followed for at least 1039 days.

m is the number of subjects that experienced a certain event in the interval 1097-1461 days; n is the number of subjects who experienced at least one MAE in the

interval, underwent a secondary procedure within 1461 days, or were followed for at least 1404 days.

m is the number of subjects that experienced a certain event in the interval 1462-1826 days; n is the number of subjects who experienced at least one MAE in the

interval, underwent a secondary procedure within 1826 days, or were followed for at least 1769 days.

Sites captured multiorgan failures using a single adverse event code. Multiorgan failure events are included in this table as they can involve respiratory or renal failure. In this table, multiorgan failure events were not counted in either respiratory complications or renal complications fields to avoid reporting the same events multiple times.

Spinal cord ischemia is related to either partial (paraparesis) or total paralysis of the lower extremities (paraplegia). As a result, site-reported events of spinal cord ischemia, paraplegia, and paraparesis were merged into the same field.

4.5% (6/133)

2.3% (3/133)

1.5% (2/133)

3.0% (4/133)

2.3% (3/133)

3.0% (4/133)

3.8% (5/133)

0.8% (1/133)

0.0% (0/133)

0.8% (1/133)

0.0% (0/133)

0.8% (1/133)

1.5% (2/133)

12.8% (17/133)

8.3% (11/133)

28.6% (38/133)

0.8% (1/124)

3.2% (4/124)

1.6% (2/124)

3.2% (4/124)

4.8% (6/124) 5.3% (6/114)

2.6% (3/114)

0.9% (1/114)

1.8% (2/114)

0.9% (1/114)

2.6% (3/114)

0.0% (0/114)

0.0% (0/98)

4.1% (4/98)

1.0% (1/98)

2.0% (2/98)

0.0% (0/98)

3.1% (3/98)

0.0% (0/124)

1.8% (2/114)

8.8% (10/114)

5.3% (7/133)

3.2% (4/124)

5.6% (7/124)

0.8% (1/124)

1.6% (2/124)

11.3% (14/124)

0.8% (1/124)

4.8% (6/124)

3.2% (4/124)

0.8% (1/124)

21.8% (27/124)

8.2% (8/98)

0.0% (0/114)

0.9% (1/114)

5.3% (6/114) 2.0% (2/98)

0.9% (1/114)

4.4% (5/114)

1.8% (2/114)

0.0% (0/98)

1.0% (1/98)

5.1% (5/98)

28.1% (32/114) 23.5% (23/98)

Figure 82. Summary of MAEs through 5 Years

Instructions for Use English 57

As part of the postapproval study, data for aneurysm ruptures and conversion to open surgery for the subjects in the IDE cohort was collected through 5 years. A detailed discussion

IDE Primary Effectiveness Endpoint

Within Expanded Analysis Window

% (m/n)

(lower endpoint of 1-sided 95% CI)

Successful Aneurysm Treatment

)%4.39( )511/211( %4.79 shtnom 21 ta

m is the number of subjects confirmed with successful aneurysm treatment; n is the total implanted subjects.

Change

1-month to 6-month

1-month to 12-month

1-month to 24-month

1-month to 36-month

1-month to 48-month

1-month to 60-month

Increase >5mm

% (m/n)

1.9% (2/108)

3.8% (4/105)

6.2% (5/81)

3.8% (3/79)

6.1% (4/66)

10.7% (6/56)

No Change ±5mm

% (m/n)

72.2% (78/108)

60.0% (63/105)

48.1% (39/81)

49.4% (39/79)

39.4% (26/66)

41.1% (23/56)

Decrease >5mm

% (m/n)

25.9% (28/108)

36.2% (38/105)

45.7% (37/81)

46.8% (37/79)

54.5% (36/66)

48.2% (27/56)

One subject experienced a Type I Endoleak. One subject experienced aneurysm growth in absence of endoleak

(endotension). Both aneurysm growth events are new to this interval.

One subject experienced a Type I Endoleak. Three subjects experienced aneurysm growth in absence of endoleak

(endotension). These four aneurysm growth events are new to this interval.

One subject experienced a Type I Endoleak. Four subjects experienced aneurysm growth in absence of endoleak (endotension). Three of these aneurysm growth events were continuing from the 12-month interval; two were new to this interval.

All three subjects experienced aneurysm growth in absence of endoleak (endotension). One aneurysm growth event was continuing from the 12-month interval; one was continuing from the 24-month interval; one was new to this interval.

One subject experienced a Type I Endoleak. Three subjects experienced aneurysm growth in absence of endoleak (endotension). One aneurysm growth event was continuing from the 24-month interval; one was continuing from the 36-month interval; two were new to this interval.

One subject experienced a Type I Endoleak. Five subjects experienced aneurysm growth in absence of endoleak (endotension). One aneurysm growth event was continuing from the 24-month visit; two from the 48-month visit; three were new to this interval.

of the results for these endpoints is provided below.

Aneurysm Ruptures through 5 Years

A total of 1.3% of subjects (2/160) experienced thoracic aneurysm ruptures. The first subject experienced multiple endoleaks and a thoracic aneurysm rupture 605 days after index implant, which was successfully treated via a secondary procedure (an additional endograft was deployed in the aneurysm). The second subject had a type “unknown” endoleak and aneurysm rupture at 1,062 days after the index procedure, resulting in death.

Conversion to Open Surgery through 5 Years

A total of 0.6% of subjects (1/160) underwent conversion to open surgery. One subject was converted to open surgery 1,112 days after the index procedure. A thoracic aneurysm expansion (when compared to 24-month) was identified at the 36-month follow-up visit in the absence of any observable endoleaks. Per the investigator's discretion the subject was converted to surgery. The investigator's discretion was based on the physician's judgment about the type of treatment that benefits the patient the most. Factors that affect this decision generally include an analysis of complexity of procedure (eg, duration, time in ICU, overall hospital stay), other procedural measurements (eg, blood loss, amount of imaging contrast), risk profile of procedure-related adverse events (eg, procedural mortality, graft infection), and longer-term clinical outcome (eg, aneurysm rupture).

6.3.12. Primary Effectiveness Endpoints

The primary effectiveness endpoint for the IDE study, successful aneurysm treatment at 12 months, was 97.4%. Successful Aneurysm Treatment was a composite endpoint that included the absence of: a) aneurysm growth of more than 5 mm at the 12-month visit relative to the 1-month visit; and b) secondary procedure due to type I or III endoleak performed or recommended at or before the 12-month visit.

Figure 83. Summary of IDE Primary Effectiveness Endpoint : Valiant Test Group

There were three subjects considered treatment failures in the Valiant Test Group. Two subjects were found to have aneurysm growth of more than 5 mm and had secondary procedures after 365 days (Figure 85). One subject had a distal type Ib endoleak for which a secondary procedure was recommended at the 12-month visit and subsequently performed after 365 days.

As part of the postapproval study, data on aneurysm growth and secondary endovascular procedures for the subjects in the IDE cohort was collected through 5 years, as detailed below.

Changes in Aneurysm Diameter through 5 Years

Changes in aneurysm diameter at the protocol follow-up intervals are presented in Figure 84 as reported by the site. In the study protocol, aneurysm expansion is defined as an increase greater than 5 mm in maximum aneurysm diameter as measured on appropriate imaging, as compared to the 1-

month follow-up imaging. Measurements were taken from visits within protocol defined windows. If there were multiple records within one visit interval, the visit closest to the target date was used. The target dates are 30 days from the initial implant procedure for the one-month visit; 183 days for the six-month visit; 365 days for the 12-month visit, etc.

Any given subject may show multiple times in the table, as his/her aneurysm growth may continue across multiple visit intervals. Overall, 24 thoracic aneurysm enlargement events in 12 subjects were identified at study visit intervals. Of these subjects, five were treated via secondary procedures. These subjects

were included in the secondary procedure section. Endoleaks of different types were reported for four of the 12 subjects. These subjects were included in the Endoleak section. Eight subjects experienced either endotension (aneurysm growth in absence of observable endoleaks due to pressurization of aneurysm) or imaging quality did not allow endoleak detection. Overall, aneurysm growth in four subjects were resolved with treatment; two, resolved without treatment; four, unresolved at time of study exit; and two, unresolved at time of death. Please note that the denominator is the number of subjects with evaluable data, whereas the numerator is the number of subjects with observations per column heading.

Secondary Endovascular Procedures through 5 Years

Secondary procedures are defined as additional procedures that are required to achieve successful treatment of the aneurysm at a time beyond initial implantation, including deployment of a secondary graft within the primary graft or balloon dilatation of anchor zones. Secondary procedures are shown in Figure 85. A total of 13 secondary endovascular procedures were performed in 11 subjects. Nine subjects had a single secondary procedure. Two subjects had two additional endovascular procedures each. In all secondary procedures, subjects were treated via deployment of additional stent grafts within the primary prosthesis.

58 Instructions for Use English

Figure 84. Changes in Aneurysm Diameter through 5 Years (Site Reported)

Type I endoleak

Aneurysm expansion

Aneurysm rupture

Other endoleak(s)

Cause of Secondary Procedure

(Investigator Assignment)

375

392

608

791

811

1,152

All secondary procedures involved placement of additional stent grafts.

This subject had two secondary endovascular interventions. One at 375 days after the initial endovascular treatment; another one 608 days after the initial endovascular treatment.

This subject had two secondary endovascular interventions. One at 392 days after the initial endovascular treatment; another one 1064 days after the initial endovascular treatment.

1,214

1,415

1,467

1,586

Time to Secondary

Procedure (days)

01/19/2009

01/31/2008

07/23/2008

01/31/2008

12/20/2007

02/27/2007

07/02/2008

07/23/2008

07/24/2008

05/16/2008

06/17/2008

10/5/2007

05/24/2007

Date of Implant

1,064

Figure 85. Secondary Endovascular Procedures through 5 Years

6.3.13. Secondary Effectiveness Endpoints

A summary of secondary IDE effectiveness endpoints is presented in Figure 86. In addition to these secondary endpoints, an evaluation of stent graft integrity was also performed. No subject had loss of stent graft integrity within 12 months.

Instructions for Use English 59

IDE Secondary Endpoints

VALIANT TEST GROUP

% (m/n)

TALENT CONTROL GROUP

% (m/n)

Successful deployment and delivery of the stent graft at implant

1,9

96.3% (154/160)

99.5% (194/195)

:syad 03 nihtiW

Secondary procedure due to endoleak after discharge

0.6% (1/157) 0% (0/194)

:shtnom 21 nihtiW

Endoleak at 12 months

2,3

)321/51( %2.21 )001/31( %31

)4001/3( %3 I epyT 4.9% (6/123)

)5001/7( %7 II epyT 4.9% (6/123)

)6001/1( %1 III epyT 0% (0/123)

)001/0( %0 VI epyT

0% (0/123)

)7001/2( %2 nwonknu / V epyT 2.4% (3/123)

Secondary endovascular procedure due to endoleak after 30 days and within 365 days

0% (0/143) 6.5% (12/186)

Migration of the stent graft at 12 months relative to 1 month

2,3

2.9% (3/105) 3.9% (4/103)

Proximal stent graft migration >10 mm proximally

)301/0( %0 )501/0( %0

Proximal stent graft migration >10 mm distally

0% (0/105) 1.9% (2/103)

Distal stent graft migration >10 mm proximally

2.8% (3/105)8 1.9% (2/103)

)301/0( %0 )501/0( %0 yllatsid mm 01> noitargim tfarg tnets latsiD

Loss of patency of the stent graft

2,3

)701/0( %0 )001/0( %0

Site reported.

Core laboratory reported.

The follow-up windows for these endpoints are similar.

Three subjects had distal type Ib endoleak; 1 subject had a secondary procedure after 365 days, a second subject withdrew consent at day 609 post index procedure, and a third subject had no additional clinical sequelae related to endoleak. Of the 2 active subjects, both were alive at the most recent follow-up visit.

One subject had 2 additional endovascular procedures and was alive at the 24-month visit; 1 subject died of lung cancer at day 593 post index procedure; 1 subject died in a motor vehicle accident at day 679 post index procedure. The other 4 subjects had no clinical sequelae related to endoleak and were alive at the most recent study visit.

One subject had type III endoleak reported by the core laboratory at the 12-month interval. No endoleak was reported by the investigational site though the 24-month visit and the subject had no clinical sequelae related to endoleak. There was no separation of stent graft components. No loss of stent graft integrity was reported by core laboratory, though the 6- and 12-month x-ray images could not be evaluated for stent graft integrity. There was no site-reported loss of stent graft integrity through the 24-month visit.

One subject had endoleak of unknown type resolved at the 24-month visit following reduction of antiplatelet therapy; endoleak of unknown type again noted at the 36-month visit. Another subject had no clinical sequelae related to endoleak of unknown type.

None of these 3 subjects had clinical sequelae related to stent graft migration. Two of the 3 subjects had limited or no remaining stent graft coverage of the distal nonaneurysmal neck.

Defined as attaining vessel access, to insert the delivery catheter and deployment of the graft to the intended treatment site. If the thoracic treatment site cannot be accessed with the delivery catheter, it is considered a technical failure. Six subjects had unsuccessful deployment or delivery. Three of these six subjects did not receive a Valiant device due to access failure. Two other subjects had misaligned deployment, and one subject had an aortic rupture.

As part of the postapproval study, data for endoleaks, migration, and loss of patency for the subjects in the IDE cohort was collected through 5 years. A discussion of the results of these endpoints evaluated from 0 through 5 years is provided below. Please note that the results discussed below are part of the postapproval monitoring. As a result, data for endoleaks presented in Figure 86 (captured and monitored during the IDE period of VALOR II) differs from data for endoleaks presented in Figure 87 (captured and monitored during postapproval portion of the study). Likewise, the source for information on migrations in Figure 86 is the CEC-adjudicated data (per IDE requirements), whereas the source for information on migrations in Figure 87 is site-reported data. As a result, the information in these two tables is different for the same period of time (specifically data through 1 year).

Endoleaks through 5 Years

Figure 87 summarizes site-reported endoleaks and device-specific safety measurements. It is possible for a subject to experience multiple types of endoleaks or a persistent endoleak across multiple follow-up intervals, so the same subject may appear across multiple timeframes and endoleak categories.

A total of 13 subjects experienced 15 type I endoleaks. The details are presented below. Of these events, 13 were distal and 2 were proximal. Endoleaks of any type in 9 subjects were treated via secondary endovascular procedures. Of note, three of these subjects experienced five type I endoleaks events with aneurysm enlargement. Additionally, two subjects experienced type IV endoleaks. These 2 events were reported by a single clinical site. Both occurred during the procedure and resolved without treatment by the first month with no adverse sequelae. The subjects did not experience aneurysm enlargement throughout their participation in the study. Similarly, one subject experienced a single type III endoleak. The cause/sub-type of this type III endoleak is unknown. This endoleak was reported at procedure, had no clinical sequelae, and was reported as resolved at the 1-month visit in absence of treatment. This subject did not experience aneurysm enlargement throughout his participation in the study.

Figure 86. IDE Secondary Endpoints

60 Instructions for Use English

Event

Any Endoleak Type

Loss of patency

Migration (> 10mm from 1-month)

Loss of integrity

Type I

Type II

Type III

Type IV

Type V/Unknown

Type Ia (proximal)

Type Ib (distal)

17.9% (25/140)

3.6% (5/140)

0.7% (1/140)

2.9% (4/140)

10.7% (15/140)

0.7% (1/140)

1.4% (2/140)

0.0% (0/140)

0.0% (0/147)

N/A

Through 1-

month visit

% (m/n)

6.7% (9/134)

2.2% (3/134)

0.7% (1/134)

1.5% (2/134)

4.5% (6/134)

0.0% (0/134)

0.7% (1/134)

0.0% (0/134)

0.0% (0/138)

0.0% (0/144)

> 1-month visit to 12-

month visit

% (m/n)

6.1% (6/98)

3.1% (3/98)

0.0% (0/98)

3.1% (3/98)

1.0% (1/98)

0.0% (0/98)

2.0% (2/98)

0.0% (0/98)

0.0% (0/99)

0.0% (0/111)

> 12-month

visit to 24-

month visit

% (m/n)

5.2% (4/77)

2.6% (2/77)

0.0% (0/77)

2.6% (2/77)

0.0% (0/77)

2.6% (2/77)

0.0% (0/77)

0.0% (0/92)

0.0% (0/98)

> 24-month

visit to 36-

month visit

% (m/n)

4.1% (3/73)

2.7% (2/73)

0.0% (0/73)

2.7% (2/73)

0.0% (0/73)

1.4% (1/73)

0.0% (0/73)

0.0% (0/69)

0.0% (0/83)

> 36-month

visit to 48-

month visit

% (m/n)

> 48-month

visit to 60-

month visit

% (m/n)

1.7% (1/60)

0.0% (0/60)

0.0% (0/

)

0.0% (0/

)

1.7% (1/60)

0.0% (0/

)

0.0% (0/60)

0.0% (0/61)

0.0% (0/70)

In VALOR II, endoleaks were reported as adverse events, regardless of clinical sequelae. This table shows the endoleaks reported at different intervals (ie, new observations), excluding continuing endoleaks during each interval. Endoleaks of any type in nine subjects were treated via secondary endovascular procedures. Of note, several of these endoleaks did not result in aneurysm enlargement.

13 subjects experienced 15 Type I endoleaks. A total of 8 were recovered with treatment; 2, recovered without treatment; 3, unresolved at time of death; and 2, continued at time of study completion. The median duration for treated Type I endoleaks was 176 days. Three subjects experienced aneurysm enlargement events (one subject at 6 months, one subject at both 12 and 24 months and one subject at both 48 and 60 months).

One subject experienced a type III endoleak, recovered without treatment 12 days after onset. This Type III endoleak was observed post-procedure, but was not seen at discharge or follow-up. This subject did not experience any aneurysm enlargement events.

Two subjects experienced type IV endoleaks. In both instances, endoleaks were observed at the end of the procedure. One of them was resolved without treatment by discharge (10 days later) and the other one was resolved without treatment by the one month visit (27 days later). These endoleaks were not observed in further follow-up visits. The subjects did not experience any aneurysm enlargement events.

Eight subjects experienced unknown endoleak types (observable endoleak from unknown origin). Four of these endoleaks remained unresolved at time of subject death; two, continued at time of study exit; and two were recovered without treatment (33 and 670 days after onset). Endotension events (aneurysm growth in absence of observable endoleak) were captured as aneurysm enlargement.

Figure 87. Endoleaks and Additional Device-Specific Safety Measures through 5 Years

]IC %59[ )n/m( %

]%001-%9.29[ )05/05( %001 tnalpmi ta tnemyolped dna yreviled lufsseccuS

Patency, Integrity, and Additional Device-Specific Safety Measures through 5 Years

As shown in Figure 87, per clinical site data, there were no occurrences of loss of stent graft patency, stent graft migration, loss of stent graft integrity, device dilatation, stent graft extrusion/erosion, stent graft infection, and stent graft thrombosis throughout the study.

6.3.14. Study Strengths and Weaknesses

The main strength of the VALOR II study is the robustness of data that resulted from 100% monitoring of clinical data, independent CEC adjudication of deaths, longer-term data from IDE subjects, and multiple audits by the FDA at different clinical sites and sponsor facilities. The limitation of this study is that it had approximately 80% follow-up compliance rate despite sponsor’s efforts to maximize compliance throughout the study.

6.4. Valiant Captivia OUS Registry

The Valiant Captivia OUS Registry began when the Valiant thoracic stent graft with the Captivia delivery system received CE mark in September 2009. The objective of this ongoing registry is to gather pertinent postapproval clinical data to assess the Valiant thoracic stent graft with the Captivia delivery system (“Valiant Captivia”) in the treatment of diseases of the descending thoracic aorta in both surgical and non-surgical candidates. Subjects diagnosed with a variety of thoracic aortic diseases were considered candidates for the registry. Subjects who enrolled in the study will be followed for up to 3 years post-implantation. A 30-day interim analysis was conducted on 50 subjects to assess acute performance of the Captivia delivery system.

6.4.1. Study Population and Subject Accountability

These 50 subjects, hereafter referred to as the Registry Study Group, were enrolled in Europe and Turkey to participate in the Valiant Captivia OUS Registry. Only the 30-day analysis for the Registry Study Group was included. Of the 50 subjects who underwent repair using the Valiant thoracic stent graft with the Captivia delivery system, 25 (50%) were indicated for thoracic aortic aneurysm (TAA), 20 (40%) were indicated for Type B aortic dissection, and 8 (16%) were classified as “Other”. Three of the subjects who are included in the “Other” category also had a concurrent thoracic aortic aneurysm or Type B aortic dissection, and are therefore included in more than 1 category. Since the acute deliverability of the delivery system is less dependent upon the type of aortic etiology, subjects with dissection and other etiologies were also considered relevant to the assessment.

Three subjects died and 1 subject was converted to open surgical repair within 30 days. No subjects were lost to follow-up or withdrew consent. Thirty-four of the 45 eligible subjects had a follow-up visit at 30 days post-implant. All of the remaining 11 eligible subjects were alive and underwent clinical evaluations at subsequent follow-up visits.

6.4.2. Successful Delivery and Deployment

Delivery and deployment of Valiant Captivia was evaluated at 30-days for the Valiant Captivia OUS Registry. Successful delivery and deployment was defined as deployment of the Valiant thoracic stent graft in the planned location with no unintentional coverage of the left subclavian artery, left common carotid artery or brachiocephalic artery, and with the removal of the delivery system.

Successful delivery and deployment was achieved in all 50 enrolled subjects in the Registry Study Group, yielding a rate of 100% (95% CI 92.9%-100%).

6.4.3. Secondary Study Endpoints

Secondary study endpoints evaluated in the 30-day analysis included both procedural complications and clinical outcomes. A summary of secondary endpoints is presented in Figure 89.

Three subjects died within 30 days of the index procedure. The CEC adjudicated 2 of the 3 deaths as due to causes other than cardiac or neurological. The first subject was treated for a symptomatic TAA and died from multi-organ failure. The second subject was treated for a TAA and subsequently died from a ruptured AAA. This subject, who had risk factors for neurologic complications, also experienced paraplegia that resolved 2 days later after placement of a lumbar drain. A third death occurred in a subject with a history of Marfan’s syndrome and previous thoracic aortic dissection. The death was adjudicated as being related to the lesion in an acute complicated type B dissection.

One subject required a conversion to open surgery following aneurysm rupture at the index procedure. The subject became unstable after the first stent graft was successfully delivered and deployed. The subject underwent a thoracotomy and a second stent graft was placed, successfully sealing off the rupture site. The subject was alive at 30 days.

Figure 88. Successful Delivery and Deployment: Valiant Captivia OUS Registry

Instructions for Use English 61

Two subjects, including the subject with Marfan’s syndrome noted above, experienced aortic dissection within 30 days of the index procedure. Both events occurred in subjects

Secondary Endpoints

)n/m( % Misaligned Deployment at Index Procedure (Site reported) 0% (0/50) Aortic Perforation at Index Procedure 0% (0/50) Death

Mortality Within 30 Days 6% (3/50) Paraplegia/Paraparesis

)05/1( %2 noitatnalpmi-tsop syaD 03 nihtiW aigelparaP

)05/0( %0 noitatnalpmi-tsop syaD 03 nihtiW siseraparaP Secondary Endovascular Procedure due to Endoleak

)05/0( %0 noitatnalpmi-tsop syad 03 nihtiw One or more Major Adverse Events (MAE)

)05/21( %42 noitatnalpmi-tsop syad 03 nihtiw sEAM ynA

One or more Serious Major Adverse Events2

)05/11( %22 noitatnalpmi-tsop syad 03 nihtiw sEAM suoireS ynA

Death and rupture were adjudicated by CEC; all other categories were reported by the investigational sites.

A serious MAE is defined as a MAE that was identified as a Serious Adverse Event (SAE) by the Investigator.

Secondary Endpoints % (m/n)

Misaligned Deployment at Index Procedure

)9/0( %0

Aortic Perforation at Index Procedure

)9/0( %0

Death

Mortality within 30 Days

)01/1( %01

Paraplegia/Paraparesis

Paraplegia within 30 Days1 Paraparesis within 30 Days

20% (2/10)

0% (0/10)

kaelodnE ot eud erudecorP ralucsavodnE yradnoceS

within 30 days post-implantation

)01/0( %0

)EAM( stnevE esrevdA rojaM erom ro enO

within 30 days post-implantation

)01/4( %04

)EAM( stnevE esrevdA rojaM suoireS erom ro enO

within 30 days post-implantation

)01/4( %04

CEC reported

Site reported

treated for Type B aortic dissection.

Figure 89. Secondary Endpoints: Valiant Captivia OUS Registry

6.5. Talent Captivia Study

In another study of the Captivia delivery system, 10 subjects were enrolled in a modified open arm of the US IDE evaluation of the Talent thoracic stent graft system in the treatment of patients with thoracic aortic disease. Disease etiologies included fusiform aneurysms and saccular aneurysms/penetrating ulcers of the descending thoracic aorta. A 30-day analysis was conducted on 10 subjects to assess the acute performance of the Captivia delivery system. The data collected from this evaluation was considered relevant because the delivery systems for use with Talent and Valiant stent grafts are essentially identical in design and possess the same principles of operations.

6.5.1. Study Population and Subject Accountability

These 10 subjects with descending aortic aneurysms were enrolled at 4 sites in the United States to participate in the Talent Captivia Study. Of the 10 enrolled subjects, 1 subject died and another failed to receive a stent graft. No subject was lost to follow-up or withdrew consent.

6.5.2. Successful Delivery and Deployment

Delivery and deployment of the Talent thoracic stent graft with the Captivia delivery system was assessed. Implantation of the device was successful in 9 of 10 enrolled subjects, yielding a rate of 90% (95% CI 55.5%-99.7%). Successful delivery and deployment was defined as attaining vessel access to insert the delivery catheter and deployment of the graft to the intended treatment site. One enrolled subject did not receive a Talent thoracic stent graft, as the Captivia delivery system could not reach the targeted lesion due to severe angulation of the thoracic aortic arch. This subject was converted to an open surgical repair.

6.5.3. Secondary Study Endpoints

Secondary study endpoints evaluated in the 30-day analysis included both procedural complications and clinical outcomes. A summary of the results are provided in Figure 90. One subject died within 30 days of the index procedure and was considered an aneurysm related death. The CEC adjudicated the death as due to cardiac causes. This subject and

1 other experienced paraplegia within 30 days. Both subjects who experienced paraplegia had significant risk factors for spinal cord ischemia.

Figure 90. Secondary Endpoints: Talent Captivia Study

7. Patient Selection and Treatment

7.1. Individualization of Treatment

Each Valiant stent graft with the Captivia delivery system must be ordered in a size appropriate to fit the patient’s anatomy. Proper sizing of the device is the responsibility of the physician. Refer to Recommended Device Sizing (Section 10.2).

Caution: Vessel damage such as dissection, perforation, or rupture may be caused by excessive oversizing of the stent graft in relation to the diameter of the blood vessel. Oversizing of the stent graft to the vessel more than the recommended device sizing as shown in Recommended Device Sizing (Section 10.2), may be unsafe, especially in the presence of dissecting tissue or intramural hematoma. Excess or insufficient oversizing may also result in Type 1 endoleak. Also, due to the nature of the design and the flexibility of the Valiant thoracic stent graft with the Captivia delivery system, the overall length of each stent graft component may be shorter when deployed.

If preoperative case planning measurements are not certain, an inventory of system lengths and diameters necessary to complete the procedure should be available to the physician. This approach allows for greater intraoperative flexibility to achieve optimal procedural outcomes. Use of the device outside the recommended anatomical sizing may result in serious device related events.

Physicians may consult with a Medtronic representative to determine proper stent graft component dimensions based on the physician’s assessment of the patient’s anatomical measurements. However, the final treatment decision is at the discretion of the physician and patient. The benefits and risks previously described should be carefully considered for each patient before using the Valiant thoracic stent graft with the Captivia delivery system.

Patient selection factors to be assessed should include, but are not limited to:

patient age and life expectancy

•

comorbidities (eg, cardiac, pulmonary, or renal insufficiency prior to surgery, morbid obesity)

•

patient’s suitability for open surgical repair

•

patient’s anatomical suitability for endovascular repair

•

the risk of lesion rupture compared to the risks of endovascular repair

•

62 Instructions for Use English

ability to tolerate general, regional, or local anesthesia

•

iliac or femoral access vessel morphology, such as thrombus, calcium formation, or tortuosity, that is compatible with vascular access techniques, devices, or accessories

•

aortic diameter in the range of 18 to 42 mm (TAA), 18 to 44 mm (BTAI), or 20 to 44 mm (dissection)

•

aortic proximal and distal neck lengths ≥20 mm (fusiform and saccular aneurysms/penetrating ulcers), landing zone ≥20 mm proximal to the primary entry tear (BTAI,

•

dissection) (the proximal extent of the landing zone must not be dissected)

8. Patient Counseling Information

The physician should review the following information when counseling the patient about this endovascular device and procedure:

Differences between endovascular repair and open surgical repair

•

■

Risks related to open surgical repair

■

Risks related to endovascular repair

Pros and cons of open surgical repair and endovascular repair

•

Endovascular repair is an option with potential advantages related to its minimally invasive approach

•

It is possible that subsequent endovascular or open surgical repair of the lesion may be required

•

The long-term effectiveness of endovascular repair has not been established

•

Regular follow-up, including imaging of the device, should be performed at least every 6 to 12 months, or more frequently in subjects with enhanced surveillance needs. For

•

more information, see Follow-up Imaging Recommendations (Section 13). Details contained in the patient information booklet regarding possible complication after implantation of the device, such as cardiac or neurological complications.

•

Symptoms of aortic rupture.

•

Medtronic recommends that the physician disclose to the patient, in written form, all risks associated with treatment using the Valiant thoracic stent graft with the Captivia delivery system. The list of potential risks occurring during and after implantation of the device are provided in Adverse Events (Section 5). Medtronic also recommends that detailed patient specific risks also be discussed. Additional counseling information can be found in the Patient Information Booklet.

9. How Supplied

9.1. Sterility

Each Valiant thoracic stent graft is individually contained within a Captivia delivery system. The Captivia delivery system is sterilized using electron beam sterilization and is supplied sterile for single use only.

Do not reuse or attempt to resterilize.

•

If the device is damaged or the integrity of the sterilization barrier has been compromised, do not use the product and contact your Medtronic Vascular representative for

•

return information.

9.2. Contents

One Valiant thoracic stent graft with the Captivia delivery system

•

One Device Registration Packet

•

9.3. Storage

Store the system at room temperature in a dark, dry place.

10. Clinical Use Information

10.1. Physician Training Requirements

All physicians should complete in-service training prior to using the Valiant thoracic stent graft with the Captivia delivery system. Caution: The Valiant thoracic stent graft with the Captivia delivery system should only be used by physicians and medical personnel trained in vascular interventional techniques and

in the use of this device. The following are the knowledge and skill requirements for physicians using the Valiant thoracic stent graft with the Captivia delivery system:

natural history of thoracic lesions and comorbidities associated with repair

•

radiographic, fluoroscopic, and angiographic image interpretation

•

angioplasty

•

appropriate use of anticoagulants (ie heparin)

•

appropriate use of radiographic contrast material

•

embolization

•

endovascular stent graft placement

•

femoral cutdown, arteriotomy, and repair

•

live fluoroscopic and angiographic image interpretation

•

nonselective and selective guidewire and catheter techniques

•

snare techniques

•

techniques to minimize radiation exposure

•

device selection and sizing

•

arterial cutdown, arteriotomy, and repair or percutaneous access and closure techniques

•

10.2. Recommended Device Sizing

Medtronic recommends that the Valiant thoracic stent graft with the Captivia delivery system be used according to the sizing guidelines in Table 3 through Table 9. If preoperative case planning measurements are not certain, an inventory of system lengths and diameters necessary to complete the procedure should be available to the physician. This approach allows for greater intraoperative flexibility to achieve optimal procedural outcomes. Use of the device outside the recommended anatomical sizing may result in serious device related adverse events or clinical incident.

The specific stent graft diameter used for treatment should be oversized relative to the nondiseased vessel using the sizing guidelines to ensure appropriate radial fixation. Strict adherence to the sizing guidelines is expected when selecting the appropriate device size. Table 3 to Table 9 describe the stent graft to vessel oversizing guidelines. Appropriate oversizing has already been incorporated into the recommended sizes. Additional oversizing should not be incorporated. Sizing outside of this range can result in endoleak, fracture, migration, infolding, or graft wear.

Caution: Oversizing of the stent graft to the vessel by more than 10% may be unsafe in the presence of dissecting tissue or intramural hematoma. Caution: Proper sizing of the Valiant thoracic stent graft is the responsibility of the physician. This stent graft sizing incorporates the recommended device oversizing for anatomical

dimension and was based on in-vitro test data. When multiple stent grafts are needed to exclude the target lesion, and the component junction or overlapping connection is not supported by the aorta (ie, in the TAA sac), the

diameter of the inside component should be oversized by 4 mm relative to the outside component. If it is supported by the vessel, oversizing to the supporting native vessel should be

Instructions for Use English 63

used, as described in Table 3 to Table 9. In order to provide the appropriate oversizing at a component junction that is not supported by the vessel and at the distal landing zones, Closed Web Tapered configurations may need to be used.

The order of deployment when using multiple stent graft configurations may vary, depending on the diameter of the aorta proximal to and distal to the lesion. Table 2 should be followed to determine the order of deployment when using multiple stent graft configurations.

Caution: When treating acute dissections with multiple devices, it is recommended to deploy the proximal device first. Inadvertent pressurization of the false lumen may result in retrograde dissection.

Note: If the vessel diameter and condition require variable proximal and distal diameter configurations, the smallest diameter stent graft should be placed first, either at the proximal or distal end of the lesion. The most proximal component must be a FreeFlo configuration. FreeFlo Tapered configurations are sized to the proximal aortic inner diameter; Closed Web Tapered configurations are sized to the distal aortic inner diameter.

Caution: A FreeFlo or Bare Spring Straight end should never be placed inside the covered section of another stent graft.

Table 2. Order of Deployment When Using Multiple Stent Graft Component Sections

Proximal Aortic Diameter < Distal Aortic Diameter

Proximal Main Section implanted at proximal end of lesion

Distal Main Section implanted with correct oversizing at junction.

Distal Extension (which is not tapered) to telescope to properly fit diameter of distal landing zone

First Section Implanted (Primary Section)

Second Section Implanted (Additional Section)

Third Section Implanted (Additional Sec-

Proximal Aortic Diameter = Distal Aortic Diameter

Proximal Main Section implanted at proximal end of lesion

Distal Main Section implanted with correct junction oversizing. Due to tapered configuration of distal main section, this fits a straight aorta correctly.

[Optional] Additional Distal Main Sections or extensions implanted with correct oversizing at junction.

Proximal Aortic Diameter > Distal Aortic Diameter

Distal Main Section (or other configuration if more appropriate) implanted at distal end of lesion

Proximal Main Section implanted with correct oversizing at junction with Distal Main Section. Proximal telescoping of devices fits this shape of aorta.

[Optional] Additional Proximal Main Sections or extensions to telescope to fit greater proximal diameter better.

tion)

Use this option when implanting the proximal section first to avoid oversizing beyond the recommendations in Table 3 to Table 9

Correct sizing of the aorta and iliac or femoral vessels must be determined before implantation of the Valiant thoracic stent graft with the Captivia delivery system. Medtronic recommends a Computed Tomography Angiogram (CTA) be performed within 3 months of the implantation. These images should be available for review during the procedure.

10.2.1. Fusiform and Saccular Aneurysms and Penetrating Ulcers Sizing Guidelines

Table 3. FreeFlo Straight Configuration (Proximal Component) Sizing Guidelines

OD (Fr)

Proximal x Distal Diameter (mm) Covered Length (mm) Proximal Native Vessel Inner

Diameter (mm)

Suggested Sizing for Unsuppor-

ted Junction with Graft Sizes

from Column 2 (mm)

22 22x22 100, 150 18, 19 26

24x24 20, 21 28 26x26 22, 23 30 28x28 24, 25 32 30x30 100, 150, 200 25, 26, 27 34 32x32 27, 28, 29 36

24 34x34 29, 30, 31 38

36x36 31, 32 40 38x38 33, 34 42 40x40 35, 36 44

25 42x42 37, 38 46

44x44 39, 40 46x46 41, 42

Table 4. FreeFlo Tapered Configuration (Proximal Component) Sizing Guidelines

(Fr) Proximal x Distal Diameter (mm) Covered Length (mm) Proximal Native Vessel Inner

Diameter (mm)

Suggested Sizing for Unsuppor-

ted Junction with Graft Sizes

from Column 2 (mm)

22 26x22 150 22, 23 26

28x24 24, 25 28 30x26 25, 26, 27 30 32x28 27, 28, 29 32

24 34x30 29, 30, 31 34

36x32 31, 32 36 38x34 33, 34 38 40x36 35, 36 40

25 42x38 37, 38 42

44x40 39, 40 44 46x42 41, 42 46

64 Instructions for Use English

Table 5. Closed Web Straight Configuration (Distal Component) Sizing Guidelines

OD (Fr) Proximal x Distal Diameter (mm) Covered Length (mm) Native Vessel Inner Diameter (mm) Suggested Sizing for Unsupported Junction with Graft Sizes from

22 22x22 100, 150 18, 19 26

24 34x34 29, 30, 31 38

25 42x42 37, 38 46

OD (Fr)

Proximal x Distal Diameter (mm) Covered Length (mm) Native Vessel Inner Diameter (mm) Suggested Sizing for Unsupported Junction with Graft Sizes from

22 22x22 100 18, 19 26

24 34x34 29, 30, 31 38

25 42x42 37, 38 46

(Fr) Proximal x Distal Diameter (mm) Covered Length (mm) Distal Native Vessel Inner Diameter (mm) Suggested Sizing for Unsupported Junction with Graft Sizes

22 26x22 150 18, 19 26

24 34x30 25, 26, 27 34

25 42x38 33, 34 42

10.2.2. BTAI Sizing Guideline

24x24 20, 21 28 26x26 22, 23 30 28x28 24, 25 32 30x30 100, 150, 200 25, 26, 27 34 32x32 27, 28, 29 36

36x36 31, 32 40 38x38 33, 34 42 40x40 35, 36 44

44x44 39, 40 46x46 41, 42

Table 6. Distal Bare Spring Straight Configuration (Distal Component) Sizing Guidelines

24x24 20, 21 28 26x26 22, 23 30 28x28 24, 25 32 30x30 25, 26, 27 34 32x32 27, 28, 29 36

36x36 31, 32 40 38x38 33, 34 42 40x40 35, 36 44

44x44 39, 40 46x46 41, 42

Table 7. Closed Web Tapered Configuration (Distal Component) Sizing Guidelines

28x24 20, 21 28 30x26 22, 23 30 32x28 24, 25 32

36x32 27, 28, 29 36 38x34 29, 30, 31 38 40x36 31, 32 40

44x40 35, 36 44 46x42 37, 38 46

Table 8. Sizing Guidelines for Treatment of Blunt Traumatic Aortic Injury

Vessel Suggested Graft Oversizing

Native

(mm) (mm) (mm)

18 22 4 19 22 3 20 22 2 21 22 1 22 24 2 23 24 1 24 26 2 25 26 1 26 28 2 27 28 1 28 30 2 29 32 3 30 32 2 31 34 3 32 34 2 33 36 3 34 36 2 35 38 3 36 38 2 37 40 3

Column 2 (mm)

from Column 2 (mm)

Instructions for Use English 65

Native Vessel Suggested Graft Oversizing

(mm) (mm) (mm)

38 40 2 39 42 3 40 42 2 40 44 4 41 44 3 42 44 2 42 46 4 43 46 3 44 46 2

10.2.3. Dissection Sizing Guideline

Appropriate oversizing has already been incorporated into the recommended sizes. Additional oversizing should not be incorporated. Oversizing of the stent graft to the vessel >10% may be unsafe in the presence of dissecting tissue or intramural hematoma.

Table 9. Sizing Guidelines for Treatment of Dissections

Native Vessel

(mm) (mm) (mm)

20 22 2 21 22 1 22 24 2 23 24 1 24 26 2 25 26 1 26 28 2 27 28 1 28 30 2 29 32 3 30 32 2 31 34 3 32 34 2 33 36 3 34 36 2 35 38 3 36 38 2 37 40 3 38 40 2 39 42 3 40 42 2 40 44 4 41 44 3 42 44 2 42 46 4 43 46 3 44 46 2

Suggested Graft Oversizing

10.3. Device Inspection

Inspect the device and packaging to verify that damage or defect does not exist. If the “Use by” date has elapsed, the device is damaged, or the sterilization barrier has been compromised, do not use the device and contact a Medtronic Vascular representative for return or replacement.

10.4. Additional Equipment Recommended

an inventory of system lengths and diameters, if preoperative case planning measurements are not certain

•

one additional Valiant thoracic stent graft with the Captivia delivery system with the size intended for implantation

•

two additional Valiant thoracic stent grafts with the Captivia delivery systems sized one size smaller and one size larger than intended size for implantation

•

assorted angiographic, angioplasty, and graduated pigtail catheters

•

radiopaque contrast media

•

fluoroscope with digital angiography capabilities and the ability to record and recall all imaging

•

surgical suite in the event that emergency open conversion surgery is necessary

•

heparin and heparinized saline solution

•

transesophageal echocardiography (TEE)

•

intravascular ultrasound catheter (IVUS)

•

introducer sheaths

•

power injector

•

radiopaque ruler

•

Reliant stent graft balloon catheter and other materials recommended in the Reliant stent graft balloon catheter's Instructions for Use

•

sterile lubricant

•

an assortment of stiff 0.035 in (0.89 mm) diameter guidewires, ≥260 cm in length

•

11. Implant Instructions

11.1. Anatomical Criteria

Patients to receive endovascular treatment must have Iliac or femoral artery access vessel morphology is compatible with vascular access techniques, devices, or accessories. Nonaneurysmal aortic diameter must be in the range of 18 mm to 42 mm (fusiform and saccular aneurysms/penetrating ulcers), or 18 mm to 44 mm (blunt traumatic aortic injuries), or

66 Instructions for Use English

20 mm to 44 mm (dissections). Nonaneurysmal aortic proximal and distal neck lengths must be ≥20 mm (fusiform and saccular aneurysms/penetrating ulcers). The landing zone must be ≥20 mm proximal to the primary entry tear (blunt traumatic aortic injuries, dissections). The proximal extent of the landing zone must not be dissected.

Caution: Landing the proximal end of the device in dissected tissue could increase the risk of damage to the septum and could lead to new septal tears, aortic rupture, retrograde dissection, or other complications

11.2. Vascular Access

1. Establish vascular access for introducing the Captivia delivery system via a small oblique groin incision over the primary access artery. Iliac conduits may be used to ensure the safe insertion of the delivery system. A secondary access site should be used for diagnostic and imaging purposes. The secondary access site is determined at the discretion of the physician.

2. To reduce the risk of thromboembolism, it is recommended that patients be anticoagulated for the duration of the procedure to achieve an ACT of 250 to 300 seconds at the discretion of the physician. Antiplatelet therapy may also be administered at the discretion of the physician.

Caution: Never advance or retract equipment from the vasculature without visualization.

11.3. Initial Angiogram

1. Using continuous fluoroscopy, traverse a 0.035 in (0.89 mm) guidewire and graduated pigtail angiographic catheter (via the secondary access site) to confirm the target landing zones.

2. Using angiographic imaging, confirm preoperative CT measurements. See Valiant thoracic stent graft sizing guidelines (Table 3 to Table 9) to confirm device diameter.

3. Leave the angiographic catheter in place during the procedure to aid in confirming the position of the graft.

Note: In order to enhance visualization of the thoracic aortic arch, an angulation of 45 to 60 degrees Left Anterior Oblique (LAO) should be chosen. Note: For dissections, it is also advisable to use transesophageal echocardiography (TEE) or intravascular ultrasound (IVUS).

11.4. Preparation of the Valiant Thoracic Stent Graft with the Captivia Delivery System

1. Carefully inspect all product packaging for damage or defects prior to use. Do not use if the “Use by” date has elapsed, the device is damaged, or the sterilization barrier has been compromised.

2. While holding the Valiant thoracic stent graft with the Captivia delivery system upright, flush the graft cover using a syringe with heparinized saline solution via the sideport (tapping the sheath to aid in releasing air bubbles). If difficult to flush, continue to apply pressure to the syringe, allowing time for saline to infuse the stent graft.

3. Flush the guidewire lumen with heparinized saline solution via the luer connector. Caution: Do not grip the tip capture release handle during flushing of the delivery system.

4. (For the FreeFlo stent graft delivery system only) Verify that the tip capture release handle is in its locked position. In its locked position, as indicated in Figure 91, the handle should not be able to rotate clockwise. See Tip Capture Release Handle in Locked Position (Figure 91).

Figure 91. Tip Capture Release Handle in Locked Position

Caution: Initiating deployment of the stent graft with the tip capture release handle in its unlocked position (rotated counterclockwise) may result in premature release of the proximal bare stent of the FreeFlo configurations.

11.5. Introducing the Captivia Delivery System

1. If necessary, open narrow entry vessels with standard PTA catheters or vessel dilators prior to Valiant thoracic stent graft implantation according to standard endovascular procedures. If necessary, dilate vessel with tapered vessel dilator. A stepup approach is recommended for vessel dilation and is at the discretion of the physician.

2. Insert the Captivia delivery system over the guidewire. Prior to insertion into the vessel, activate the hydrophilic coating by wiping the outer surface of the graft cover with a sterile gauze, saturated in saline, until the graft cover is slippery to touch.

Figure 92. Introducing the Captivia Delivery System

Note: The Captivia delivery system does not require a separate introducer sheath for the primary access site. Caution: Manipulation of wires, balloons, catheters, and endografts in the thoracic aorta may lead to vascular trauma, including aortic dissection and embolization. Caution: Do not bend, kink, or otherwise alter the Captivia delivery system prior to implantation because it may cause deployment difficulties Caution: If an obstruction in the vessel, such as a tortuous bend, stenosis, or calcification formation, prevents advancement of the Captivia delivery system, do not use excessive

force to advance the delivery system. The cause of resistance must be assessed in order to avoid vessel or delivery catheter damage.

Instructions for Use English 67

Caution: Do not grip the tip capture release handle during introduction of the delivery system.

Confirming position with Proximal

Figur8 Markers and Distal Zer0 Markers

Confirming position of overlapping grafts

with Figur8 Mid-Marker

and Distal Zer0 Marker

(An implanted FreeFlo

configuration is shown in this image)

11.6. Positioning the Captivia Delivery System

1. Slowly advance the Captivia delivery system to the targeted landing zone. For patients who do not have excessive calcification or thrombus formation, it is suggested to position the device more proximal (a few millimeters higher in the vessel) to the targeted landing zone.

2. In patients with highly tortuous anatomy, it is suggested to position the device even more proximal to the targeted landing zone, as the stent graft may move distally when the graft cover is initially pulled back, then proximally when the first stent of the stent graft is released.

Caution: It is not recommended to position the device higher in the presence of excessive calcification or thrombus, due to the increased risk of dislodging material during distal repositioning of the stent graft.

Caution: Be sure to avoid or compensate for parallax or other sources of visualization error. Caution: Do not advance the Captivia delivery system tip or guidewire across the aortic valve. Caution: Do not grip the tip capture release handle during positioning of the delivery system.

11.7. Confirming Stent Graft Position

1. Before beginning deployment of the Valiant thoracic stent graft, confirm proper position of the device using fluoroscope with digital angiography capabilities.

2. When placing the stent graft, verify that the proximal Figur8 markers are in the desired location (Figure 93). Placement of the distal end is verified by ensuring that the distal Zer0 markers are in the desired location. Additional stent grafts may be implanted to extend the length of coverage and exclude the lesion. For additional information, see Implanting Additional Configurations (Section 11.12).

Figure 93. Confirm Stent Graft Position

Note: To confirm stent graft position when implanting 2 or more Valiant devices, the minimum overlap is achieved by aligning the distal Zer0 markers of the proximal graft with the single Figur8 Mid-Marker of the distal graft. See Implanting Additional Configurations (Section 11.12).

Caution: In the presence of excessive calcification or thrombus formation, it is not recommended to position the device higher and then reposition distally after partial stent graft deployment, due to increased risk of dislodging material.

Caution: Be sure to avoid or compensate for parallax or other sources of visualization error. Caution: Do not grip the tip capture release handle while confirming the position of the delivery system.

11.8. Deploying the Valiant Thoracic Stent Graft

1. Decreasing Mean Arterial Blood Pressure (MAP) - Upon confirmation that the Captivia delivery system is positioned properly, it may be appropriate to momentarily decrease the patient’s MAP to approximately 80 mmHg (at the discretion of the physician) to avoid inadvertent displacement of the Valiant thoracic stent graft upon withdrawal of the graft cover.

2. Deploying Proximal End - First hold the delivery system stationary with 1 hand on the grey front grip. Then, slowly withdraw the graft cover with the other hand by rotating the slider handle counter-clockwise. It may take multiple rotations before the graft cover separates from the tip, visualized by movement of the radiopaque marker band. For the FreeFlo stent graft delivery system: The proximal bare stent of the FreeFlo configuration will be constrained by the tip capture mechanism. Withdraw the graft cover until up to 2 covered stents are exposed. For the Closed Web stent graft delivery system: Withdraw the graft cover until up to 2 covered (body) stents are exposed. In the unlikely event of delivery system failure and concomitant partial stent graft deployment due to graft cover severance, a “handle disassembly” technique will permit successful deployment of the stent graft. See Troubleshooting Techniques (Section 12).

Note: The Captivia delivery system should be stabilized and remain stationary during stent graft deployment.

68 Instructions for Use English

For the FreeFlo stent graft delivery system,

the proximal bare stent is constrained

by the tip capture mechanism.

For the Closed Web stent graft delivery

system, the proximal end is not

constrained.

Figure 94. Deploying the Proximal End of the Stent Graft

For the FreeFlo stent graft delivery system,

the proximal bare stent is constrained

by the tip capture mechanism.

For the Closed Web stent graft delivery

system, the proximal end is deployed.

Caution: A Closed Web configuration should never be used as the most proximally implanted stent graft. Caution: Do not place the proximal end of the covered stent graft beyond the distal edge of the left common carotid artery. Caution: If the stent graft is deployed higher than the targeted landing zone, it is important to not deploy more than 2 covered stents prior to repositioning of the stent graft.

Further deployment of the graft can impair the ability to move the graft to the desired landing zone. Repositioning of the stent graft in dissection treatment is only allowed in the region of healthy aortic tissue.

Caution: Do not release the proximal bare stent of the FreeFlo configuration before the entire stent graft has been deployed, as this may result in inaccurate deployment. Caution: Ensure that the Valiant devices are placed in a landing zone without evidence of circumferential thrombus, intramural hematoma, dissection, ulceration, or aneurysmal

3. Verifying Position - Use angiography to verify the position of the stent graft in relation to the desired location. Use the proximal Figur8 markers to aid in visualizing the proximal end of the covered stent graft. If the stent graft was deployed higher than the targeted landing zone, maintain the position of the slider handle and pull down on the entire delivery system until the proximal Figur8 markers indicating the top edge of the fabric are at the desired position.

4. Deploying Remainder of Stent Graft - Continue withdrawing the graft cover. To more rapidly deploy the stent graft, place 1 hand firmly on the grey front grip and hold the system stationary. While maintaining support on the grey front grip, pull back the grey trigger to engage the quick-release function of the blue slider handle. Pull the blue slider handle away from the grey front grip until the RO Marker Band on the graft cover is beyond the distal spring. If excessive force is felt, release the grey trigger and rotate the blue slider handle to complete deployment of the stent graft.

For the FreeFlo stent graft delivery system: At this point, the proximal bare stent is still constrained by the tip capture mechanism. For the Closed Web stent graft delivery system: At this point, the entire Closed Web stent graft has been deployed.

Note: If necessary, the stent graft can be repositioned distally to the desired location by retracting it, as long as no more than 2 of the proximal springs have been deployed. Note: Deployment of the stent graft in the aortic arch can increase the deployment force. Deployment forces can be further increased by excessive tortuosity and a small radius

aortic arch. Note: In the unlikely event of delivery system failure and concomitant partial stent graft deployment due to graft cover severance, a “handle disassembly” technique may permit

the successful deployment of the stent graft. For additional information, see Handle Disassembly Technique for Partial Stent Graft Deployment (Section 12.1). Caution: When using the trigger to rapidly deploy the stent graft, assure the grey front grip remains stationary. Failure to do so will cause movement of the stent graft position and

will result in inaccurate deployment.

Caution: Do not rotate the delivery system during deployment, as this may torque the delivery system and cause the stent graft to twist during deployment. Caution: Do not advance the Valiant thoracic stent graft with Captivia delivery system when it is partially deployed and it is apposed to the vessel wall. Caution: Once the entire covered portion of the stent graft has been deployed, do not attempt to adjust the position of the stent graft. Caution: If the graft cover is inadvertently withdrawn, the stent graft will prematurely deploy and will be placed incorrectly.

Figure 95. Deploying the Remainder of the Stent Graft

Instructions for Use English 69

11.9. Deploying Tip Capture Mechanism (on the FreeFlo System Only)

1. Continue to hold the delivery system stationary with 1 hand on the front grip.

2. With the other hand, rotate the tip capture release handle counter-clockwise to unlock the handle.

Figure 96. Unlocking the Tip Capture Release Handle

3. Pull the tip capture release handle back in a smooth motion until the tip capture mechanism is released, and the proximal bare stent of the FreeFlo configuration is completely open (Figure 97). Observe the opening of the bare stent under fluoroscopy and confirm that the proximal bare stent has been completely deployed.

Figure 97. Deploying the Tip Capture Mechanism

Note: In the unlikely event that the proximal bare stent of the FreeFlo configuration cannot be deployed, refer to Troubleshooting Techniques (Section 12). Caution: Keep the delivery system stationary while deploying the tip capture mechanism. Do not pull back on or push forward on the delivery system while deploying the tip

capture mechanism, as it may cause the entire graft to move. Caution: Do not push forward on the tip capture release handle or on the entire delivery system until the front grip has been pulled towards the slider handle. See Delivery

System Removal (Section 11.10). Doing so may cause the tip capture mechanism to get caught on the proximal bare stent.

11.10. Delivery System Removal

1. Continue to hold the Captivia delivery system with 1 hand on the front grip and the other hand on the slider.

2. Pull back the grey trigger and hold the slider handle stationary while bringing the grey front grip towards the slider handle as depicted in Figure 98. Use continual fluoroscopy and watch the proximal end of the Valiant thoracic stent graft while slowly pulling back the tapered tip into the graft cover of the delivery system. It may be necessary to pull the entire delivery system back into a straight section of the aorta to aid in retraction of the tip.

3. (FreeFlo stent graft delivery system only) After the front grip has been pulled back to rejoin the slider, push the tip capture release handle forward so that the tip capture component moves toward the RO marker band of the graft cover. Monitor the movement of the tip capture component using fluoroscopy. (Closed Web stent graft delivery system only) Proceed to Step 4.

4. Gently remove the delivery system, using fluoroscopy to ensure that the stent graft does not move during the withdrawal.

70 Instructions for Use English

Figure 98. Delivery System Removal

Caution: Carefully monitor the retrieval of the tapered tip with fluoroscopy to ensure that the tip does not cause the Valiant thoracic stent graft to be inadvertently pulled down.

11.11. Smoothing Stent Graft Fabric and Modeling the Stent Graft

Caution: Never use a balloon when treating a dissection.

Reliant stent graft balloon catheter can be used to assist in stent graft implantation by modeling the covered springs and to remove wrinkles and folds from the graft material (Figure 99). Refer to the Instructions for Use supplied with the Reliant stent graft balloon catheter for more information.

Note: Care should be taken when inflating the balloon, especially with calcified, tortuous, stenotic, or otherwise diseased vessels. Inflate slowly. It is recommended that a backup balloon be available.

Figure 99. Balloon Modeling of the Stent Graft

Warning: Do not use the Reliant stent graft balloon catheter in patients with a history of aortic dissection disease. Do not over-inflate the balloon. Warning: When expanding a vascular prosthesis using the Reliant balloon, there is an increased risk of vessel injury or rupture, and possible patient death, if the balloon’s proximal

and distal radiopaque markers are not completely within the covered (graft fabric) portion of the prosthesis.

11.12. Implanting Additional Configurations

If 2 or more Valiant thoracic stent graft configurations are required to exclude the lesion, follow the steps below. Caution: When treating acute dissections with multiple devices, it is recommended to deploy the proximal device first. Inadvertent pressurization of the false lumen may result in

retrograde dissection. Caution: FreeFlo Tapered and Straight and Bare Spring Straight stent graft configurations should never be placed inside the graft covered section of another graft as doing so may

result in abrasion of the fabric by the bare spring, resulting in graft material holes or broken sutures. Caution: A Closed Web Tapered or Straight configuration may be implanted as the primary section only when implanting multiple stent grafts in a nontortuous segment of the

descending thoracic aorta with the distal-to-proximal implantation technique.

Caution: Failure to provide sufficient overlap may result in separation of stent graft components. Note: In vitro durability (fatigue) testing may suggest that the long-term durability of the device may be compromised in conditions with excessive device oversizing or deformation

associated with cardiac and respiratory cycles. Wire fractures may have unknown clinical consequences which may include, but are not limited to; device migration, vessel perforation, loss of aneurysm exclusion, false lumen enlargement, or death.

1. Refer to Preparation of the Valiant thoracic stent graft with the Captivia delivery system (Section 11.4).

2. Refer to Introducing the Captivia Delivery System (Section 11.5). Advancement of the delivery system within the previously implanted stent graft must be carefully monitored under fluoroscopy to ensure that the implanted stent graft does not move.

3. Refer to Positioning the Captivia Delivery System (Section 11.6).

4. Refer to Confirming Stent Graft Position (Section 11.7). Radiographically verify that the Zer0 markers on the proximal graft align with the single Figur8 (between the third and fourth covered spring) on the distal graft to achieve the minimum overlap distance (Figure 93, Figure 100, and Figure 101). Also, verify that the markers on the additional stent graft indicate that the proximal and distal ends of the covered stent graft are at the desired locations.

Instructions for Use English 71

Minimum overlap is achieved by aligning the Zer0 marker on the proximal section with the Figur8 Mid-Marker on the distal section.

Figure 100. Alignment of Additional Sections (First Graft Placed Proximally)

Minimum overlap is achieved by aligning the Zer0 marker on the proximal section with the Figur8 Mid-Marker on the distal section.

Figure 101. Alignment of Additional Sections (First Graft Placed Distally)

1. Proximal Figur8 Marker

2. Figur8 Mid-Marker

3. Minimum Required Overlap

4. Distal Zer0 Marker

5. Refer to Deploying the Valiant Thoracic Stent Graft (Section 11.8).

6. If the additional section is a FreeFlo Straight or Tapered configuration stent graft, refer to Deploying Tip Capture Mechanism (Section 11.9).

7. Refer to Delivery System Removal (Section 11.10).

8. Refer to Smoothing Stent Graft Fabric and Modeling the Stent Graft (Section 11.11).

11.13. Angiogram

Upon completion of the implant procedure, perform angiography to verify stent graft apposition, seal, and any endoleaks at the proximal and distal ends of the stent graft. Assess the stent graft for mid-graft and graft junction endoleaks.

Perform adjunctive maneuvers as needed, such as ballooning or insertion of additional devices. The most reliable course of endoleak management (Type I or Type III) is by remodeling the stent graft with a balloon and, if needed, placing an additional stent graft (Section 11.11 and Section 11.12). A minor leak that does not seal after re-ballooning may seal spontaneously within several days. If any adjunctive maneuvers are conducted, perform a final angiogram to confirm successful exclusion of the lesion.

Caution: Do not use a balloon catheter to treat aortic dissection. Caution: High pressure injections at the edges of the Valiant thoracic stent graft immediately after implantation may cause acute endoleaks. Caution: Any endoleak left untreated during the implantation procedure must be carefully monitored after implantation.

11.14. Entry Site Closure

Remove all remaining accessories (for example, guidewire, introducer sheath, or angiogram catheter). Close the arteriotomy site by standard surgical closure techniques.

72 Instructions for Use English

12. Troubleshooting Techniques

Imaging Modality

Visit

Angiogram CTA/MRA

1,2,3

Chest X-ray

)lanoitpo( X erudecorP-erP

X larudecorP

htnoM 1 X

)retfaereht yllaunna( htnoM 21 X

CT evaluation may include 3-D reconstruction, volume measurements, or computer-aided measurements.

A six-month follow-up with CT Scan and Chest X-ray are recommended if an endoleak is reported at 1 month after

the procedure.

Magnetic resonance angiogram (MRA) or a CT without contrast may be used in patients with impaired renal function or

intolerance to contrast media at the discretion of the physician

Pretreatment assessment should be done within 3 months prior to treatment.

If a Type I or III endoleak is present, prompt intervention and additional follow-up post-intervention is recommended.

12.1. Handle Disassembly Technique for Partial Stent Graft Deployment

In the unlikely event of delivery system failure and concomitant partial stent graft deployment due to graft cover severance, a “handle disassembly” technique may permit the successful deployment of the stent graft.

1. Pull back the trigger and fully retract the slider. Note: Since the graft cover is severed, the slider can be retracted without further deploying the stent graft.

2. Stabilize the delivery system.

3. Insert the tips of a pair of hemostats into each of the handle disassembly ports on the front grip.

4. Disengage the front grip from the screw gear by pressing the tips of the hemostats into the handle disassembly ports and simultaneously advancing the front grip away from the screw gear.

5. Advance the front grip until it fully clears the screw gear.

6. Separate the screw gear halves in order to identify the location of graft cover severance.

7. Grip the graft cover manually or with hemostats and retract until the stent graft is fully deployed.

8. (FreeFlo stent graft delivery system only) Deploy the tip capture mechanism (Section 11.9).

9. Remove the delivery system by gripping the screw gear and withdrawing from the patient.

12.2. Alternative Instruction for Deploying Tip Capture Mechanism

In the unlikely event of delivery system failure and non-release of the tip capture mechanism due to tip capture tube severance, an alternative technique may permit the successful release of the proximal bare stent.

1. Ensure the delivery system remains stationary and continue to monitor stent graft position.

2. Remove the back end lock by turning counter-clockwise and pulling off of the delivery system. It may be necessary to push the tip capture release handle forward to gain access to the back end lock.

3. Pull the tip capture release handle back as far as it can go.

4. Using a hemostat, separate the halves of the tip capture release handle and discard

5. Remove the clamping ring by turning clockwise and pulling off of the delivery system.

6. Separate the screw gear halves at the back end in order to identify the location of tip capture tube severance. The tip capture tube is the brown tube from which the guidewire lumen emerges.

7. While holding the luer connector and guidewire lumen steady, grip the tip capture tube with hemostats and retract it until the proximal bare stent is fully released from the tip capture mechanism.

8. Hold the delivery system with one hand on the front grip and the other hand on the slider. Pull back the trigger and hold the slider stationary while bringing the front grip towards the slider as depicted in Delivery System Removal (Figure 98).

9. Gently remove the delivery system while maintaining backwards tension on the guidewire lumen to keep the tapered tip seated within the graft cover. Use fluoroscopy to ensure that the stent graft does not move during the withdrawal.

13. Follow-up Imaging Recommendations

13.1. General

All patients should be advised that endovascular treatment requires lifelong, regular follow-up to assess their health and the performance of their endovascular graft. Patients with specific clinical findings (e.g., endoleaks, enlarging aneurysms, enlarging false lumens, or changes in the structure or position of the endovascular graft) should receive additional follow-up. Patients should be counseled on the importance of adhering to the follow-up schedule, both during the first year and at yearly intervals thereafter. Patients should be informed that regular and consistent follow-up is a critical part of ensuring the ongoing safety and effectiveness of endovascular treatment of thoracic aortic lesions. This includes fusiform aneurysms, saccular aneurysms, penetrating atherosclerotic ulcers, transections, and dissections. Physicians should evaluate patients on an individual basis and prescribe follow-up relative to the needs and circumstances of each individual patient.

Annual imaging follow-up may include chest X-ray and computed tomography angiogram (CTA), with and without contrast.

The combination of contrast and non-contrast CT imaging provides information on aneurysm diameter change, false lumen diameter change, endoleak, patency, tortuosity,

•

progressive disease, fixation length and other morphological changes The chest X-rays provide information on device integrity (separation between components and stent fracture)

•

Figure 102 lists the recommended imaging follow-up for patients with the Valiant thoracic stent graft. Ultimately, it is the physician’s responsibility, based on previous clinical results and the overall clinical picture, to determine the appropriate imaging schedule for a particular patient.

Figure 102. Imaging Recommendations

13.2. Angiographic Imaging

Angiographic images are recommended at pretreatment (within 3 months of implant) for centers without CTA 3-D reconstruction capabilities to assist in determining anatomic suitability. Angiographic images are also recommended during the treatment to evaluate anatomy and device placement.

13.3. CTA Images

CTA images are recommended pretreatment to determine anatomic suitability for the Valiant thoracic stent graft. CTA with 3-D reconstruction is recommended in order to accurately assess the patient’s anatomy. The physician will determine the required pre-operative care for patients with allergies to contrast or who have impaired renal function.

CTA images are also recommended post-treatment for lesion and device assessment. The triphasic imaging protocol for follow-up CT should consist of an unenhanced, contrast enhanced, and 5 minute delay scan. Refer to CTA Imaging Guidelines (Table 10) for optimal CTA results. MRA may be used at the physician's discretion.

Film sets should include all sequential images at the lowest possible slice thickness (<3 mm). Do not perform large slice thickness (>3 mm) or omit consecutive CT images or

•

films sets, as this prevents precise anatomical and device comparisons over time.

Instructions for Use English 73

Both non-contrast and contrast runs are required, with matching or corresponding table positions.

•

Pre-contrast and contrast run slice thicknesses and intervals must match.

•

Do not change patient orientation or relandmark the patient between non-contrast and contrast runs.

•

Non-contrast and contrast enhanced baseline and follow-up imaging are important for optimal patient surveillance. Table 10 lists examples of accepted imaging protocols.

Table 10. CTA Imaging Guidelines

Injection Volume (cc or mL) 100–150 Injection Rate (cc/sec or mL/sec) 3–4 via 20G IV or larger (4–5 for obese pts >220 lbs (99.8 kg)) Bolus Timing SmartPrep, Carebolus, or equivalent Scan Range Thoracic inlet to aortic bifurcation Scan Diameter (FOV) Large DFOV (cm) 24–30 Scan Type Helical Rotation Speed (sec) 0.8 Slice Thickness (mm) ≤2.5 Scan Mode HS Table Speed (mm/rot) 15 Interval (mm) 1 kVp 120 mA 120 for non-contrast/200 for contrast portion of study Reconstruction (mm) 1 (normal body habitus) to 2 (>220 lbs (99.8 kg))

13.4. X-ray

Chest X-rays should be used to assess device integrity such as stent graft fracture or separation between components. Posterior/Anterior (PA) and lateral images are recommended for visualization of the stent graft. Ensure the entire device is captured on images for device assessment.

13.5. MRI/MRA Information

Patients with impaired renal function (i.e., renal insufficiency) may also be considered for magnetic resonance imaging (MRI) or angiography (MRA) at the discretion of the physician. Artifact may occur related to the stent, and care should be used to insure adequate imaging of the outer aortic wall to assess TAA or false lumen size. Volume measurement may be helpful if the aneurysm or false lumen is not clearly shrinking. If there are concerns regarding imaging of calcified areas, fixation sites, or the outer wall of the aneurysm sac or false lumen, adjunctive CT without contrast may be needed.

Nonclinical testing has demonstrated that the Valiant stent graft is MR Conditional. A patient with this device can be safely scanned in an MR system meeting the following conditions:

Static magnetic field of 1.5 or 3.0 tesla only

•

Maximum spatial gradient magnetic field of 1000 gauss/cm or less

•

Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 4 W/kg (First Level Controlled Mode)

•

Under the scan conditions defined above, the Valiant stent graft is expected to produce:

a maximum temperature rise of <1ºC after 15 minutes of continuous scanning in both a 1.5 tesla scanner and a 3.0 tesla scanner.

•

The image artifact extends approximately 5 mm and 13 mm from the device, both inside and outside the device lumen when scanned in nonclinical testing using the sequence: spin echo and gradient echo, respectively, in a 3.0 tesla GE Signa HDx MR system with a whole body coil.

13.6. Supplemental Imaging

Note: Additional radiological imaging may be necessary to further evaluate the stent graft in situ based on findings revealed by previous imaging assessments. The following

recommendations may be considered.

If there is evidence of poor or irregular position of the stent graft, severe angulation, kinking, or migration of the stent graft on chest X-rays, a spiral CT should be performed to

•

assess aneurysm or false lumen size and the presence or absence of an endoleak. If a new endoleak, increase in TAA size, or increase in false lumen size is observed by spiral CT, adjunctive studies such as 3-D reconstruction or angiographic assessment

•

of the stent graft and native vasculature may be helpful in further evaluating any changes of the stent graft or lesion. Spiral CT without contrast, MRI or MRA may be considered in select patients who cannot tolerate contrast media or who have renal function impairment. For centers with

•

appropriate expertise, gadolinium or CO2 angiography may be considered in patients with renal function impairment requiring angiographic assessment.

14. Additional Surveillance and Treatment

Additional endovascular repair or open surgical repair should be considered for patients with evidence of enlarged aneurysm (>5 mm), endoleak, false lumen enlargement, migration, inadequate seal zone, or fracture.

Consideration for reintervention or conversion to open repair should include the attending physician’s assessment of an individual patient’s comorbidities, life expectancy, and the patient’s personal choices. Patients should be counseled that subsequent reintervention may become necessary following an endograft procedure. This may include catheter-based or open surgical conversion.

15. Device Registration

The Valiant thoracic stent graft with the Captivia delivery system is packaged with additional specific information which includes:

Temporary Device Identification Card that includes both patient and stent graft information. Physicians should complete this card and instruct the patient to keep it in their

•

possession at all times. The patients should refer to this card anytime they visit additional healthcare practitioners, particularly for an additional diagnostic procedure (e.g. MRI). This temporary identification card should only be discarded when the permanent identification card is received.

Device Tracking Form to be completed by the hospital staff and forwarded to Medtronic for the purposes of tracking all patients who received a Valiant thoracic stent graft

•

(as required by Federal Regulation). The hospital’s submission of the device tracking form to Medtronic is also required for a patient to receive the permanent identification card.

Upon receipt of the completed Device Tracking Form, Medtronic will mail the patient a Permanent Device Identification Card. This card includes important information regarding the implanted stent graft. Patients should refer to this card anytime they visit healthcare practitioners, particularly for any diagnostic procedures (eg, MRI). Patients should carry this card with them at all times. If a patient does not receive their permanent device identification card, or requires changes to the card, call 1-800-551-5544. In addition a patient information booklet (PIB) will be provided to the physicians during training and additional copies will be available upon request. The PIB will also be available online on the Medtronic website (www.medtronic.com). This booklet provides patients with basic information on lesions of the descending aorta and endovascular repair therapy.

16. MRI Safety Information

Nonclinical testing has demonstrated that the Valiant thoracic stent graft is MR Conditional. It can be scanned safely in 1.5 T and 3.0 T MR systems only, using only specific testing parameters (Section 13.5). Additional MRI safety information is found in Section 13.5.

Disclaimer of Warranty

ALTHOUGH THE VALIANT THORACIC STENT GRAFT WITH THE CAPTIVIA DELIVERY SYSTEM, HEREAFTER REFERRED TO AS “PRODUCT”, HAS BEEN MANUFACTURED UNDER CAREFULLY CONTROLLED CONDITIONS, MEDTRONIC, INC., AND AFFILIATES (COLLECTIVELY, “MEDTRONIC”) HAVE NO CONTROL OVER CONDITIONS UNDER

74 Instructions for Use English

WHICH THIS PRODUCT IS USED. THE WARNINGS CONTAINED IN THE PRODUCT LABELING PROVIDE MORE DETAILED INFORMATION AND ARE CONSIDERED AN INTEGRAL PART OF THIS DISCLAIMER OF WARRANTY. MEDTRONIC THEREFORE DISCLAIMS ALL WARRANTIES, BOTH EXPRESSED AND IMPLIED, WITH RESPECT TO THE PRODUCT, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTY OR MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, SHALL NOT BE LIABLE TO ANY PERSON OR ENTITY FOR ANY MEDICAL EXPENSES OR ANY DIRECT, INCIDENTAL, OR CONSEQUENTIAL DAMAGES CAUSED BY ANY USE, DEFECT, FAILURE, OR MALFUNCTION OF THE PRODUCT, WHETHER A CLAIM FOR SUCH DAMAGES IS BASED UPON WARRANTY, CONTRACT, TORT, OR OTHERWISE. NO PERSON HAS ANY AUTHORITY TO BIND MEDTRONIC TO ANY REPRESENTATION OR WARRANTY WITH RESPECT TO THE PRODUCT.

The exclusions and limitations set out above are not intended to, and should not be construed so as to, contravene mandatory provisions of applicable law. If any part or term of this disclaimer of warranty is held to be illegal, unenforceable, or in conflict with applicable law by a court of competent jurisdiction, the validity of the remaining portions of this disclaimer of warranty shall not be affected, and all rights and obligations shall be construed and enforced as if this disclaimer of warranty did not contain the particular part or term held to be invalid.

Instructions for Use English 75

Medtronic, Inc.

*M333320F001*

710 Medtronic Parkway Minneapolis, MN 55432 USA Tel: (763) 514-4000 Fax: (763) 514-4879 www.medtronic.com

US CUSTOMER SERVICE/PRODUCT INQUIRIES:

Tel: (800) 961-9055 Fax: (800) 929-2133

Protected by one or more of the following United States patents: 6,306,141; 6,344,052; 6,911,039; 7,105,016; and 7,264,632.

Medtronic VAMC2424C100TU Instructions for Use

Specifications and Main Features

Frequently Asked Questions

User Manual

1. Device Description

1.1. Stent Graft

1.1.1. Stent Graft Configuration Options

1.2. Delivery System

2. Indications for Use

3. Contraindications

4. Warnings and Precautions

4.1. General

4.2. Patient Selection

4.3. Implant Procedure

4.4. MRI Safety Information

5. Adverse Events

5.1. Potential Adverse Events

5.2. Adverse Event Reporting

6. Summary of Clinical Studies

6.1. Medtronic Dissection Trial

6.1.1. Suitability of the Performance Goal

6.1.2. Subject Accountability and Follow-up

6.1.3. Subject Population Demographics and Baseline Parameters

6.1.4. Valiant Thoracic Stent Graft Usage

6.1.5. Acute Procedural Data

6.1.6. Safety and Effectiveness Results

6.1.7. Data Post 12 Months

6.1.8. Overall Conclusions

6.2. RESCUE

6.2.1. Clinical Endpoints

6.2.2. Accountability of PMA Cohort

6.2.3. Subject Population Demographics and Baseline Parameters

6.2.4. Valiant Thoracic Stent Graft Usage

6.2.5. Acute Procedural Data

6.2.6. Safety and Effectiveness Results

6.2.7. Effectiveness Results

6.2.8. Overall Conclusions

6.3. VALOR II

6.3.1. VALOR II IDE

6.3.2. VALOR II Postapproval Study

6.3.3. Data collected Preapproval and Postapproval

6.3.4. Subject Accountability and Follow Up through 5 years

6.3.5. Study Demographics and Baseline Medical History

6.3.6. Baseline Aneurysm Data

6.3.7. Devices Implanted

6.3.8. Acute Procedural Data

6.3.9. Clinical Utility Data

6.3.10. Primary Safety Endpoints

6.3.11. Secondary Safety Endpoints

6.3.12. Primary Effectiveness Endpoints

6.3.13. Secondary Effectiveness Endpoints

6.3.14. Study Strengths and Weaknesses

6.4. Valiant Captivia OUS Registry

6.4.1. Study Population and Subject Accountability

6.4.2. Successful Delivery and Deployment

6.4.3. Secondary Study Endpoints

6.5. Talent Captivia Study

6.5.1. Study Population and Subject Accountability

6.5.2. Successful Delivery and Deployment

6.5.3. Secondary Study Endpoints

7. Patient Selection and Treatment

7.1. Individualization of Treatment

8. Patient Counseling Information

9. How Supplied

9.1. Sterility

9.2. Contents

9.3. Storage

10. Clinical Use Information

10.1. Physician Training Requirements

10.2. Recommended Device Sizing

10.2.1. Fusiform and Saccular Aneurysms and Penetrating Ulcers Sizing Guidelines

10.2.2. BTAI Sizing Guideline

10.2.3. Dissection Sizing Guideline

10.3. Device Inspection

10.4. Additional Equipment Recommended

11. Implant Instructions

11.1. Anatomical Criteria

11.2. Vascular Access

11.3. Initial Angiogram

11.4. Preparation of the Valiant Thoracic Stent Graft with the Captivia Delivery System