VenaSeal™
Closure System
Instructions for Use
Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.
The following list includes trademarks or registered trademarks of Medtronic in the United States and possibly in other countries. All other trademarks are the property of their respective owners.
ClosureFast, Covidien, Medtronic, VenaSeal
Definition of symbols
Sterilized using ethylene oxide
Lot number
Consult instructions for use at this website
Use-by date
Do not use if package is damaged
Keep dry
Manufacturer
Catalog number
Caution: Federal law (USA) restricts this device to sale by or on the order of a physician
Sterilized using steam or dry heat
Do not reuse
Do not resterilize
Nonpyrogenic
Straight floppy tip guidewire
Quantity
3
Contents
1 Device description ................................................................................................. 5
2 Indications for use ................................................................................................. 5
3 Contraindications ................................................................................................. 5
4 Warnings and Precautions ............................................................................................ 5
4.1 Warnings ...................................................................................................... 5
4.2 Precautions ..................................................................................................... 5
5 Potential adverse events ............................................................................................. 5
6 Summary of clinical studies ........................................................................................... 6
7 Primary clinical study (VeClose) ........................................................................................ 6
7.1 Study design .................................................................................................... 6
7.2 Clinical inclusion and exclusion criteria ..................................................................................... 6
7.3 Study population demographics and baseline parameters ......................................................................... 7
7.4 Procedural data .................................................................................................. 8
7.5 Safety and effectiveness results ......................................................................................... 8
8 How supplied ................................................................................................... 10
9 Storage ....................................................................................................... 11
10 Directions for use ................................................................................................ 11
10.1 Recommended accessories ......................................................................................... 11
10.2 Preparation ................................................................................................... 11
10.3 Access ...................................................................................................... 11
10.4 Assembly .................................................................................................... 11
10.5 Procedure .................................................................................................... 12
10.6 If the primed catheter needs to be withdrawn from the introducer prior to completion, take the following steps: ........................................ 13
10.7 Total amounts of VenaSeal adhesive expected for use in vein treatments .............................................................. 13
11 Disposal ...................................................................................................... 14
12 Disclaimer of warranty ............................................................................................ 14
4
1 Device description
VS-404
The VenaSeal closure system is a medical device provided as a sterile, single patient kit comprised of the VenaSeal adhesive and VenaSeal delivery system components. The kit is designed
to be used as a system, and its contents are not intended for use as individual components. The VenaSeal system is intended to be used by a licensed physician while using high resolution
ultrasound imaging. The VenaSeal system is indicated for the permanent closure of lower extremity superficial truncal veins, such as the great saphenous vein (GSV), through endovascular
embolization with coaptation. The VenaSeal system is intended for use in adults with clinically symptomatic venous reflux as diagnosed by duplex ultrasound (DUS).
The VenaSeal adhesive, an n-butyl-2-cyanoacrylate (n-BCA) based formulation, is a clear, free-flowing liquid that is provided sterile following exposure to dry heat. The VenaSeal adhesive
polymerizes in the vessel via an anionic mechanism (i.e., VenaSeal adhesive begins to polymerize into a solid material upon contact with body fluids or tissue). This acute coaptation halts
blood flow through the insufficient vein until the implanted adhesive becomes fibrotically encapsulated to establish a durable, chronic occlusion of the treated vein. The VenaSeal delivery
system components facilitate the placement and delivery of VenaSeal adhesive within the target vessel. The VenaSeal delivery system components include a catheter, introducer, dilator,
dispenser gun, dispenser tips, 3 cc syringes, and 0.035 in straight floppy tip guidewire. The VenaSeal system kit is provided sterile by exposure to ethylene oxide (EtO).
Figure 1. VenaSeal closure system
2 Indications for use
The VenaSeal closure system (VenaSeal system) is indicated for use in the permanent closure of lower extremity superficial truncal veins, such as the great saphenous vein (GSV), through
endovascular embolization with coaptation. The VenaSeal system is intended for use in adults with clinically symptomatic venous reflux as diagnosed by duplex ultrasound (DUS).
3 Contraindications
Separate use of the individual components of the VenaSeal closure system is contraindicated. These components must be used as a system.
The use of the VenaSeal system is contraindicated when any of the following conditions exist:
• previous hypersensitivity reactions to the VenaSeal adhesive or cyanoacrylates
• acute superficial thrombophlebitis
• thrombophlebitis migrans
• acute sepsis
Prior to use, read all package insert warnings, precautions and instructions. Failure to do so may result in severe patient injury and/or death.
4 Warnings and Precautions
4.1 Warnings
• The VenaSeal system should only be used by a trained physician with experience in diagnosis and treatment of venous reflux disease through endovenous techniques. Physicians require
training using the VenaSeal system by the manufacturer prior to performing this procedure independently.
• Due to the risk of exposure to HIV or other blood borne pathogens, health care workers should always use standard blood and body fluid precautions in the care of all patients. Strictly
adhere to sterile techniques during any handling of the device.
• The VenaSeal system is not designed for use in the coronary and cerebral vasculature, pulmonary vasculature, or diseased and atherosclerotic arteries.
• Do not flush the catheter with saline or fluid as this will make it unusable with the VenaSeal adhesive.
• Manipulate the catheter only under ultrasound imaging guidance.
• Confirm position of the catheter tip in the desired location by ultrasound imaging before activation of the device.
• Injection of the VenaSeal adhesive should be done by hand injection only and using the VenaSeal delivery system provided. Do not use a power injector.
• Do not kink the catheter. Do not use the catheter if it is kinked.
• Use the introducer in the VenaSeal delivery system for access to the peripheral vasculature. Failure to use the introducer for access may result in damage to the vessel, or failure of the
VenaSeal system to perform as intended.
4.2 Precautions
• The safety and effectiveness of the VenaSeal system in pregnant women and in pediatric patients have not been established.
• The VenaSeal system is sterile unless the package is opened or damaged. Examine the package before using the system. If the package is damaged, do not use the system.
• The VenaSeal system is supplied sterile for single use only. Do not reprocess or resterilize. Reprocessing and resterilizing could increase the risk of patient infections and risk of
compromised device performance.
• Before using, carefully examine the VenaSeal closure system components and verify that they and their packaging have not been damaged during shipment. If the components show any
sign of damage, do not use the system.
• Do not use after the use-by date.
• Verify that the VenaSeal adhesive is a clear and free-flowing liquid prior to use. Adhesive that is discolored should be discarded.
• The VenaSeal adhesive will adhere to most surfaces. Avoid contact with non-disposable surfaces.
• Gloves and eye/face protection are recommended when handling the VenaSeal adhesive.
• The VenaSeal adhesive is intended to be delivered via the VenaSeal delivery system components only.
5 Potential adverse events
The potential adverse events (e.g., complications) associated with the use of the VenaSeal system include, but are not limited to, the following list:
5
• Adverse reactions to a foreign body (including, but not limited to, nonspecific mild inflammation of the cutaneous and subcutaneous tissue)
• Arteriovenous fistula
• Bleeding from the access site
• Deep vein thrombosis (DVT)
• Edema in the treated leg
• Embolization, including pulmonary embolism (PE)
• Hematoma
• Hyperpigmentation
• Hypersensitivity or allergic reactions to cyanoacrylates, such as urticaria, shortness of breath, and anaphylactic shock
• Infection at the access site
• Pain
• Paresthesia
• Phlebitis
• Superficial thrombophlebitis
• Urticaria, erythema, or ulceration may occur at the injection site
• Vascular rupture and perforation
• Visible scarring
6 Summary of clinical studies
The clinical evidence supporting the safety and effectiveness of the VenaSeal closure system (previously referred to as the Sapheon™ Closure System) is derived from a combination of three
clinical studies, as outlined in Table 1. The pivotal clinical study, the VeClose study, was used to establish a reasonable assurance of safety and effectiveness of treating symptomatic superficial
truncal veins with the VenaSeal system for permanent closure by embolization with coaptation of the vein walls in the United States under IDE G120204. Data from this clinical study were the
basis for the PMA approval decision (PMA P140018).
Table 1. Summary of VenaSeal closure system clinical studies
Study Title Objective
VeClose Pivotal VenaSeal Sapheon Closure System vs. Radiofrequency
eSCOPE European Sapheon Closure System Observational Prospec-
Ablation for Incompetent Greater Saphenous Veins (VeClose)
tive (eSCOPE) Study
Feasibility Sapheon™ Closure System First-In-Man Study Assess safety and effectiveness in a first in man setting
To demonstrate safety and effectiveness of the VenaSeal system for the treatment of lower extremity truncal reflux compared to radiofrequency ablation (RFA) performed using the
Covidien ClosureFast™ system.
To assess the role of the Sapheon Closure System in closure
of incompetent great saphenous veins in a routine clinical
setting
7 Primary clinical study (VeClose)
7.1 Study design
The VeClose pivotal study was a controlled, randomized, prospective, multicenter, pivotal study in which patients with venous reflux in the great saphenous vein (GSV) were treated with either
the VenaSeal system or radiofrequency ablation (RFA) therapy. Prior to initiation of the randomized cohort at each site, a non-randomized training cohort of 2 subjects per clinical site (roll-in
phase) was enrolled and treated with the VenaSeal system. Subjects were then randomized at each site, 1:1, as stratified by random blocks of sizes of 4 and 6.
Up to 244 subjects (including 2 roll-in subjects per clinical site [up to 12 clinical sites] and 220 randomized) with symptomatic venous reflux in the GSV were planned to be enrolled. The sample
size of 110 subjects per group in the randomized cohort was calculated assuming underlying success rates of 95% in each group, a 10% non-inferiority delta, a one-sided alpha of 0.025 and
10% loss to follow-up in each group. The 95% success rate was based on the complete occlusion rate in the feasibility study as well as individual randomized controlled trials reporting RFA
efficacy rates of 97% at 3 months1, and 100% and 95.2% at 1 month and 1 year respectively2. Adding 2 roll-in subjects per site (12 sites), the final planned sample size was 244 subjects.
Patients were treated between March 11, 2013, and September 11, 2013, with 242 patients (including 20 roll-in patients) enrolled at 10 investigational sites. Following treatment, subjects were
followed at 3 days, and 1, 3, 6, 12, 24, and 36 months. No adjunctive treatments were permitted until after the 3-month follow-up visit.
The primary objective of this study was to demonstrate safety and effectiveness of the VenaSeal system for the treatment of lower extremity truncal reflux compared to RFA therapy using a
legally marketed device with similar indications for use3. Safety was assessed by monitoring procedure-specific and systemic adverse events. A combined Data Safety Monitoring Board
(DSMB)/Clinical Events Committee (CEC) provided oversight of the study through 12 months to increase the reliability of the data and to adjudicate the study’s reported safety events.
The primary effectiveness endpoint was the proportion of subjects at 3 months with complete closure of the target GSV as determined by duplex ultrasound and adjudicated by the independent
vascular ultrasound core laboratory (Vascular Ultrasound Core Laboratory [VasCore], Massachusetts General Physicians Organization, Inc. [Boston, MA]).
The two secondary endpoints, intraoperative pain and ecchymosis at day 3, were analyzed to demonstrate standard statistical superiority of the VenaSeal system over RFA. The Holm
stepdown method was used to adjust for multiplicity in the secondary endpoint analysis. Analysis included the following items:
• Intraoperative pain experienced during the procedure (from after vein access through the end of the procedure) was rated on a 0-10 numerical rating scale (NRS) and compared across
groups using a two-tailed student’s t test.
• Ecchymosis, rated by the physician on a 0-5 scale at the day 3 visit, was compared across groups using a two-tailed Wilcoxon test.
Preoperatively, the patient’s medical history was collected, as well as demographic data and current medications. A physical examination, including assessment of ecchymosis on the target
limb, Clinical Etiology Anatomy Pathophysiology (CEAP; Classification of Venous Disorders) status and Venous Clinical Severity Score (VCSS) were performed. Quality of life data was also
collected, including the Aberdeen Varicose Vein Questionnaire (AVVQ) and EuroQol Quality of Life Questionnaire (EQ-5D). Duplex ultrasound of the target limb was conducted by the qualified
vascular or ultrasound technologist. Intraoperatively, the secondary endpoint of intraoperative pain experienced during the procedure (from after vein access through the end of the procedure)
was rated on a 0-10 numeric rating scale (NRS) by the subject. Postoperatively, the objective parameters measured during the study included the following list:
• Target GSV closure assessed by duplex ultrasound at all postoperative follow-up visits
• Procedure-related pain at day 3
• Extent of ecchymosis of the skin over the treated segment at day 3
• CEAP at all postoperative follow-up visits starting at month 3
• VCSS at all postoperative follow-up visits starting at day 3
• AVVQ and EQ-5D at all postoperative follow-up visits starting at month 1
• Subject satisfaction questionnaire at day 0 and months 3, 6, 12, 24, and 36
• Adverse events and complications at all visits
7.2 Clinical inclusion and exclusion criteria
Enrollment in the VeClose study was limited to patients who met the following inclusion criteria:
1
Nordon IM, Hinchiffe RJ, Brar R, et al. A prospective double-blind randomized controlled trial of radiofrequency versus laser treatment of the great saphenous vein in patients with varicose veins. Ann Surg. 2011;254(6):
876-81.
2
Rasmussen LH, Lawaetz M, Bjoern L, Vennits B, Blemings A, Eklof B. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great
saphenous varicose veins. Br J Surg. 2011;98(8):1079-87.
3
The ClosureFAST™ Radiofrequency Catheter (Covidien) is intended for endovascular coagulation of blood vessels in patients with superficial vein reflux (K111887).
6
1. Age ≥21 years and ≤70 years of age at the time of screening
2. Reflux in the great saphenous vein (GSV) greater than 0.5 sec reflux
3. One or more of the following symptoms related to the target vein: aching, throbbing, heaviness, fatigue, pruritus, night cramps, restlessness, generalized pain or discomfort, swelling
4. GSV diameter while standing of 3-12 mm throughout the target vein as measured by Duplex ultrasound
5. Clinical Etiology Anatomy Pathophysiology (CEAP; Classification of Venous Disorders) classification C2 (if symptomatic) to C4b
6. Ability to walk unassisted
7. Ability to attend follow-up visits
8. Ability to understand the requirements of the study and to provide informed consent
Patients were not permitted to enroll in the VeClose study if they met any of the following exclusion criteria:
1. Life expectancy <1 year
2. Active treatment for malignancy other than non-melanoma skin cancer
3. Symptomatic peripheral arterial disease with ankle brachial index (ABI) <0.89
4. Daily use of narcotic or non-steroidal anti-inflammatory pain medications to control pain associated with GSV reflux
5. Current, regular use of systemic anticoagulation (e.g., warfarin, heparin)
6. Previous or suspected deep vein thrombosis (DVT) or pulmonary embolus (PE)
7. Previous superficial thrombophlebitis in GSV
8. Previous treatment of venous disease in target limb, other than spider vein treatment
9. Known hypercoagulable disorder
10. Conditions which prevent vein treatment with either RFA or the VenaSeal system
11. Immobilization or inability to ambulate
12. Pregnant prior to enrollment
13. Tortuous GSV, which, in the opinion of the investigator, will limit catheter placement or require more than one primary access site
14. Aneurysm of the target vein with local vein diameter >12 mm
15. Significant, incompetent, ipsilateral small saphenous, intersaphenous or anterior accessory great saphenous vein(s)
16. Known sensitivity to cyanoacrylate (CA) adhesives
17. Current participation in another clinical study involving an investigational agent or treatment, or within the 30 days prior to enrollment
18. Patients who require bilateral treatment during the next 3 months
19. Patients who require additional ipsilateral treatments on the same leg within 3 months following treatment
7.3 Study population demographics and baseline parameters
A total of 242 subjects were enrolled into the study from 10 U.S. based centers, including 20 roll-in subjects treated with the VenaSeal system, 108 randomized subjects treated with the
VenaSeal system, and 114 randomized subjects treated with RFA. The demographics and baseline parameters of the study population are typical for a varicose vein study performed in the
U.S. (see Table 2 to Table 5).
Overall mean age was 50 years (range 25 to 70) and consistent with the known female predominance of venous disease, with primarily female subjects (80%). The majority of subjects (56.6%)
entered the study with venous disease in the study limb classified as C2. There were slightly more subjects with the left leg treated (53%). Aching and pain were the two most frequently reported
dominant symptoms, with over 25% of subjects reporting these symptoms. The pre-procedure mean vein diameters as assessed by ultrasound at both the proximal and mid-thigh GSV were
similar between the VenaSeal system treatment and RFA, with almost 80% of all subjects with a GSV proximal diameter of < 8 mm and over 90% of subjects with a GSV mid-thigh diameter
of < 8 mm. There were no statistically significant differences in the demographics or baseline parameters between the randomized groups (treated with either the VenaSeal system or RFA)
and the entire group treated with the VenaSeal system (randomized and roll-in subjects).
Table 2. Demographics (intent-to-treat [ITT] population)
Roll-in phase Randomized phase
Parameter
Gender
Female 17 (85%) 83 (77%) 93 (82%) 193 (80%)
Male 3 (15%) 25 (23%) 21 (18%) 49 (20%)
p-value - VenaSeal system treatment groups
p-value - Randomized 0.4821
Age (years)
Mean (SD) 53.1 (9.2) 49.0 (11.8) 50.5 (10.5) 50.1 (11.0)
Median (range) 55.1 (36 - 65) 50.3 (26 – 70) 51.8 (25 – 70) 51.2 (25 -70)
p-value - VenaSeal system treatment groups
p-value - Randomized 0.3390
Body mass index
Mean (SD) 27.9 (5.1) 27.0 (5.1) 27.0 (5.7) 27.1 (5.4)
Median (range) 27.2
p-value - VenaSeal system treatment groups
p-value - Randomized 0.9499
Ethnicity
Hispanic 0 (0%) 4 (4%) 8 (7%) 12 (5%)
Not Hispanic 20 (100%) 104 (96%) 106 (93%) 230 (95%)
p-value - VenaSeal system treatment groups
p-value - Randomized 0.4269
Race
White 19 (95.0%) 102 (94.4%) 106 (93.0%) 227 (93.8%)
Black / African American 1 (5.0%) 1 (0.9%) 4 (3.5%) 6 (2.5%)
Asian 0 (0%) 2 (1.9%) 0 (0%) 2 (0.8%)
American Indian / Alaska
Native
Other 0 (0%) 3 (2.8%) 3 (2.6%) 6 (2.5%)
p-value - VenaSeal system treatment groups
VenaSeal system (n=20) VenaSeal system (n=108) RFA (n=114) All (n=242)
0.6064
0.0927
(17.8 -37.8)
0.4860
0.8612
0 (0%) 0 (0%) 1 (0.9%) 1 (0.4%)
0.4370
26.7
(17.4 – 44.5)
26.5
(17.0 – 46.7)
26.7
(17.0 -46.7)
7
Table 2. Demographics (intent-to-treat [ITT] population) (continued)
Parameter
p-value - Randomized 0.3175
Note: Percentages are based on the number of subjects per column. P-value for VenaSeal system treatment groups compared the roll-in and randomized subjects treated with the VenaSeal
system.
Table 3. Baseline clinical CEAP status of study limb (ITT population)
Clinical classification
C2 12 (60.0%) 61 (56.5%) 64 (56.1%) 137 (56.6%)
C3 7 (35.0%) 32 (29.6%) 36 (31.6%) 75 (31.0%)
C4a 1 (5.0%) 13 (12.0%) 12 (10.5%) 26 (10.7%)
C4b 0 (0%) 2 (1.9%) 2 (1.8%) 4 (1.7%)
p-value - VenaSeal system treat-
ment groups
p-value - Randomized 0.9560
Table 4. Treatment limb characteristics (ITT population)
Parameter Roll-in phase Randomized phase
VenaSeal system (n=20) VenaSeal system (n=108) RFA (n=114) All (n=242)
Target leg
Right 11 (55%) 47 (44%) 56 (49%) 114 (47%)
Left 9 (45%) 61 (56%) 58 (51%) 128 (53%)
p-value - VenaSeal system treatment groups
p-value - Randomized 0.4825
Dominant symptom
Pain 6 (30.0%) 33 (30.6%) 24 (21.1%) 63 (26.0%)
Aching 7 (35.0%) 32 (29.6%) 39 (34.2%) 78 (32.2%)
Itching 0 (0%) 2 (1.9%) 5 (4.4%) 7 (2.9%)
Burning 0 (0%) 5 (4.6%) 3 (2.6%) 8 (3.3%)
Sensitivity 1 (5.0%) 1 (0.9%) 2 (1.8%) 4 (1.7%)
Heaviness 2 (10.0%) 14 (13.0%) 16 (14.0%) 32 (13.2%)
Swelling 2 (10.0%) 17 (15.7%) 18 (15.8%) 37 (15.3%)
Other 2 (10.0%) 4 (3.7%) 7 (6.1%) 13 (5.4%)
p-value - VenaSeal system treatment groups
p-value - Randomized 0.6536
Table 5. Pre-Procedure ultrasound measurements (ITT population)
VenaSeal system (n=20) VenaSeal system (n=108) RFA (n=114) All (n=242)
Proximal vein diameter 20 108 113
Mean (SD) (mm) 6.9 (1.6) 6.3 (2.1) 6.6 (2.1) 6.5 (2.1)
< 8 mm 14 (70.0%) 89 (82.4%) 88 (77.2%) 191 (78.9%)
≥ 8 mm 6 (30.0%) 19 (17.6%) 25 (21.9%) 50 (20.7%)
Not Done 0 (0%) 0 (0%) 1 (0.9%) 1 (0.4%)
p-value (t-test) - VenaSeal system
treatment groups
p-value (t-test) - Randomized 0.3026
Mid-Thigh vein diameter 20 107 110 237
Mean (SD) (mm) 5.3 (1.4) 4.9 (1.5) 5.1 (1.5) 5.0 (1.5)
< 8 mm 19 (95.0%) 104 (96.3%) 104 (91.2%) 227 (93.8%)
≥ 8 mm 1 (5.0%) 3 (2.8%) 6 (5.3%) 10 (4.1%)
Not Done 0 (0%) 1 (0.9%) 4 (3.5%) 5 (2.1%)
p-value (t-test) - VenaSeal system
treatment groups
p-value (t-test) - Randomized 0.2193
Roll-in phase Randomized phase
VenaSeal system (n=20) VenaSeal system (n=108) RFA (n=114) All (n=242)
Roll-in phase Randomized phase
VenaSeal system (n=20) VenaSeal system (n=108) RFA (n=114) All (n=242)
0.5785
0.4821
0.6391
Roll-in phase Randomized phase
241
0.1499
0.2759
7.4 Procedural data
The duration of the procedure, from accessing the leg through withdrawal of the catheter, and including administration of the tumescent anesthesia for the RFA subjects, averaged 24 minutes
for the VenaSeal system and 19 minutes for RFA. The mean difference in procedure duration was 5.4 minutes and this difference was statistically significant, p<0.0001. The vein access site
(above knee, below knee, at knee) distribution was similar between the VenaSeal system and RFA with slightly more VenaSeal system procedures with vein access below the knee compared
to RFA (52.8% vs 45.6%, respectively). The mean amount of lidocaine used was lower for the VenaSeal system group vs. the RFA group (1.61 vs. 2.68 cc, p = 0.0056). Mean tumescent
anesthesia volume was 272 cc in the RFA group. The mean (SD) volume of VenaSeal adhesive administered was 1.21 mL (0.41).
7.5 Safety and effectiveness results
A total of 242 patients (including 20 roll-in patients) were treated and enrolled in the VeClose study at 10 investigational sites. Following treatment, subjects were followed at 3 days, and 1,
3, 6, 12, 24, and 36 months. Safety and effectiveness data collected through month 12 formed the basis for PMA approval, and additional safety and effectiveness data was obtained at 24
and 36 months. Safety and effectiveness results cumulative through month 36 are included in this section.
7.5.1 Safety results
Safety of this study was assessed by the occurrence rate of each of the following clinically-related adverse events:
• Deep venous thrombosis (DVT)
• Clinically significant pulmonary embolus (PE)
• Paresthesia
• Skin burn
8
• Skin ulceration
• Infection/cellulitis
Through 36-month follow-up, there were no reports of deep venous thrombosis (DVT) occurring on the study limb or pulmonary embolus (PE) in the study. The incidence of paresthesia
occurring in the treatment zone was 3.1% for the subjects treated with the VenaSeal system (1 roll-in and 3 randomized) and 2.6% for the RFA group (3). The incidence of skin burn was 0%
for the subjects treated with the VenaSeal system and 0.9% for the subjects randomized to treatment with RFA. The incidence of access site infection was 0.9% for both randomized groups.
The incidence of adverse events by study-specific dictionary, all of which occurred within 12 months, is presented in Table 6.
Table 6. Incidence of adverse eventsa by study-specific dictionary
Coded term Roll-in phase (n=20) Randomized phase
VenaSeal system (n=108) RFA (n=114)
Access site burn 0 (0%) 0 (0%) 1 (0.9%)
Access site infection
Deep vein thrombophlebitis 0 (0%) 0 (0%) 1 (0.9%)
b
0 (0%) 1 (0.9%) 1 (0.9%)
c
Paresthesia in the treatment zone 1 (5.0%) 3 (2.8%) 3 (2.6%)
Paresthesia not in treatment zone 0 (0%) 0 (0%) 1 (0.9%)
Pulmonary embolus 0 (0%) 0 (0%) 0 (0%)
Skin ulceration 0 (0%) 0 (0%) 0 (0%)
a
Clinically relevant adverse events as pre-defined by the clinical protocol.
b
The protocol pre-specified adverse event assessment was “infection/cellulitis.” There was one case of cellulitis reported in an RFA-treated subject 340 days post-procedure that was reported as not related to the device
or procedure.
c
Deep vein thrombophlebitis occurred in the non-index leg.
After completion of the 36-month follow-up, a total of 45.3% subjects treated with the VenaSeal system (11 roll-in and 47 randomized) and 36.8% subjects treated with RFA (42) reported at
least 1 adverse event (AE). A total of 156 events were reported: 93 in subjects treated with the VenaSeal system (15 roll-in, 78 randomized), and 63 in subjects treated with RFA.
In addition, note the following information:
• There have been no device or procedure-related deaths or unanticipated adverse device effects reported. There was 1 death in a subject randomized to treatment with the VenaSeal
system due to liver cancer, which was reported as unrelated to the device or procedure and occurred 1098 days post-index procedure.
• There were 15 serious adverse events (SAE) reported in 12 subjects (1 roll-in, 5 treated with the VenaSeal system, and 6 treated with RFA). All SAEs were unrelated to the respective
devices and procedures.
• The Data Safety Monitoring Board (DSMB) and Clinical Events Committee (CEC) adjudicated safety events through 12-month follow-up.
• There were no reported allergic reactions to the VenaSeal adhesive (cyanoacrylate).
Two events occurred more frequently in subjects treated with the VenaSeal system (roll-in and randomized) compared to subjects treated with RFA: phlebitis (all locations) and superficial
thrombophlebitis (Table 7). Most of these events were reported by the 12-month visit. Phlebitis and superficial vein thrombophlebitis are commonly reported side effects in vein treatments,
including the VenaSeal system and RFA. These AEs were generally mild in severity and typically required either no treatment or medical treatment, consisting of typical non-steroidal
anti-inflammatory drugs (NSAID). There were 2 AEs in subjects treated with the VenaSeal system—1 for “superficial vein thrombophlebitis,” and 1 for “phlebitis not in the treatment zone” that
underwent a procedure to drain the coagulum.
Table 7. Phlebitis and superficial vein thrombophlebitis adverse events by study-specific dictionary
Coded term Roll-in (n=20) VenaSeal system (n=108) All VenaSeal system (n=128) RFA (n=114)
Phlebitis in both treatment and
non-treatment zones
0 (0.0%) 2 (1.9%) 2 (1.6%) 1 (0.9%)
Phlebitis in treatment zone 2 (10.0%) 12 (11.1%) 14 (10.9%) 10 (8.8%)
Phlebitis not in treatment zone 1 (5.0%) 11 (10.2%) 12 (9.4%) 6 (5.3%)
All Phlebitis Events 3 (15.0%) 24 (22.2%) 27 (21.1%) 17 (14.9%)
Superficial vein thrombophlebi-
tis
3 (15.0%) 6 (5.6%) 9 (7.0%) 4 (3.5%)
Note: The percentages are the proportion of subjects with each specific event.
7.5.2 Primary effectiveness results
The primary endpoint of the study was complete closure of the target vein at 3 months after index treatment as judged by the core laboratory. Complete closure was defined as duplex ultrasound
showing closure along entire treated target vein segment with no discrete segments of patency exceeding 5 cm. In instances where a month 3 duplex ultrasound exam was not available (e.g.,
images missing, unreadable, visit not done), the month 1 (or day 3) and/or month 6 duplex ultrasound images were transmitted and assessed by the core laboratory. The time points prior to
month 3 (i.e., day 3 or month 1) were used to impute missing data for the last observation carried forward (LOCF) model of the primary effectiveness endpoint.
The primary endpoint hypothesis test was performed using the intent to treat (ITT) population. For the ITT cohort, missing values were imputed using the following techniques:
• Last observation carried forward (LOCF)
• Pessimistic, which assumes that all missing data are failures for the primary endpoint
• Optimistic, which assumes that all missing data are successes for the primary endpoint
• Predictive, in which logistic regression based on selected baseline parameters, if predictive of complete occlusion, are used to predict whether the missing value is likely to be a success
or failure
Additionally, a complete case (CC) cohort analysis was performed.
Table 8 presents the results of the primary effectiveness endpoint analyses (performed with SAS) with missing data imputed by the 4 pre-specified models, as well as the CC cohort. All
pre-specified models and the CC cohort demonstrated non-inferiority of the VenaSeal system randomization arm to the RFA randomization arm.
Analyses for primary effectiveness endpoint at month 3 (ITT population)
Table 8.
Model
Success rate VenaSeal
system (n=108) Success rate RFA (n=114) Rate difference (95% CI)aP-value for non-inferioritybP-value for superiority
c
LOCF 107/108 (99.1%) 109/114 (95.6%) 3.5 (-0.7 – 7.6%) <0.0001 0.0560
Pessimistic 92/108 (85.2%) 93/114 (81.6%) 3.6 (-6.2 – 13.4%) 0.0032 0.2356
Optimistic 107/108 (99.1%) 109/114 (95.6%) 3.5 (-0.7 – 7.6%) <0.0001 0.0560
Predictive 98.9% 95.5% 3.5 (-0.8 – 7.7%) <0.0001 0.0660
CC cohort 92/93 (98.9%) 93/98 (94.9%) 4.0 (-0.8 – 8.9%) <0.0001 0.0554
a
Asymptotic confidence limits for the proportion difference
b
Wald test of non-inferiority test for the risk difference (from SAS PROC FREQ)
c
Asymptotic p-value for superiority test from StatExact Proc.
Treatment failures (> 5 cm opening in the treated vein) occurred in a total of 6 subjects (1 randomized to treatment with the VenaSeal system and 5 randomized to treatment with RFA) at month
3. A thorough review of the collected data from the treatment failures did not suggest any obvious failure mode(s). Modeling was not performed for the VenaSeal system randomization arm,
since the number of failures was too small. Recurrence of patency in treated veins is often attributed to new tributary varicosities or disease progression.
Target GSV closure assessment by the clinical site at the month 12 visit was an additional analysis for the primary effectiveness assessment. The rates of target GSV closure remained high
across both treatment groups with 92/95 (96.8%) VenaSeal system and 91/94 (96.8%) RFA.
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7.5.3 Gender analysis
The primary effectiveness endpoint was examined for differences in outcome between genders. The target GSV closure rate at month 3 by gender is shown in Table 9. No effect of gender
on the primary effectiveness endpoint was found.
Table 9. Complete closure at month 3 by core laboratory ultrasound assessment by gender (ITT population, LOCF model)
Gender Statistics Males treated with: Females treated with:
VenaSeal system RFA VenaSeal system RFA
Success Rate n (%) 25/25 (100%) 18/21 (85.7%)
Difference in Success Rate Point estimate 14.3% 0.9%
7.5.4 Secondary effectiveness results
There was less ecchymosis (i.e., bruising) at day 3 in subjects randomized to treatment with the VenaSeal system, compared to subjects randomized to treatment with RFA (p=0.0013,
Wilcoxon test). The number of subjects that experienced no ecchymosis at day 3 was greater in subjects randomized to treatment with the VenaSeal system than RFA subjects (67.6% vs.
48.2%) (Table 10). Subjects randomized to treatment with the VenaSeal system reported a mean intraoperative pain score of 2.16 (SD 2.23), and subjects randomized to treatment with RFA
reported a mean pain during treatment score of 2.35 (SD 2.18). There was no statistical significance in subject-reported pain scores (p=0.5359).
Table 10. Summary of secondary effectiveness endpoints
Endpoint description Statistic Randomization phase P-Value
VenaSeal system RFA
Pain during treatment Mean (SD)
Ecchymosis at day 3 0.0013
Note: P-value of 0.0013 represents Wilcoxon test to compare the five scales of ecchymosis at day 3 between randomization groups.
7.5.5 Additional effectiveness
Results of the VCSS, clinical classification CEAP, AVVQ, and EQ-5D demonstrated marked improvement in both the randomized group treated with the VenaSeal system and the randomized
group treated with RFA, from baseline to month 12, with no difference across treatment groups. Significant improvement was seen as early as 1 month post-procedure for VCSS, AVVQ, and
EQ-5D, with improvements sustained out to 36 months for subjects in both randomization arms.
While complete closure was based on core laboratory adjudication for the primary effectiveness endpoint, target GSV closure was assessed by the clinical site at the 3 day and 3, 6, 12, 24,
and 36-month visits using complete case (CC) analysis, as shown in Table 11. At month 3, 103/104 (99.0%) of subjects treated with the VenaSeal system and 103/108 (95.4%) of subjects
treated with RFA had target GSV closure by site assessment. The rates of target GSV closure remained high across both treatment groups at month 12 (92/95 [96.8%] of those treated with
the VenaSeal system and 91/94 [96.8%] of those treated with RFA). Long-term closure and durability was further demonstrated across both treatment groups at 36 months, with 68/72 (94.4%)
of subjects treated with the VenaSeal system and 68/74 (91.9%) of subjects treated with RFA demonstrating complete closure of the target GSV.
Table 11. Complete closure of target GSV by visit (complete case [CC] population)
Time point Roll-in (N=20) Randomization phase
VenaSeal system (N=108) RFA (N=114)
Day 3 (20/20) 100.0%
Month 1 (20/20) 100.0% (105/105) 100.0% (95/110) 86.4%
Month 3 (19/19) 100.0% (103/104) 99.0% (103/108) 95.4%
Month 6 (17/17) 100.0% (100/101) 99.0% (99/105) 94.3%
Month 12 (17/17) 100.0% (92/95) 96.8% (91/94) 96.8%
Month 24 (14/16) 87.5% (82/86) 95.3% (79/84) 94.0%
Month 36 (16/17) 94.1% (68/72) 94.4% (68/74) 91.9%
Note: Complete closure based on clinical site assessment. Closure rates through month 12 were based on data used for basis of PMA approval. Based on data availability for additional
subjects through month 36, the closure rates for RFA at month 1, month 6, and month 12 are 96/110 (87.3%), 101/105 (96.2%), and 93/97 (95.9%), respectively.
None (%) 67.6% 48.2%
< 25% (%) 26.9% 33.3%
25-50% (%) 2.8% 14.0%
50-75% (%) 1.9% 3.5%
75-100% (%) 0.9% 0.9%
2.16 (2.23) 2.35 (2.18) 0.5359
(108/108) 100.0% (113/114) 99.1%
82/83 (98.8%) 91/93 (97.8%)
8 How supplied
The VenaSeal closure system is a medical device provided as a sterile, single patient kit comprised of the VenaSeal adhesive and VenaSeal delivery system components. The kit is designed
to be used as a system, and its contents are not intended for use as individual components. The VenaSeal adhesive, an n-butyl-2-cyanoacrylate (n-BCA) based formulation, is a clear,
free-flowing liquid that is provided sterile following exposure to dry heat. The VenaSeal delivery system components facilitate the placement and delivery of VenaSeal adhesive within the target
vessel. The VenaSeal system kit is provided sterile by exposure to ethylene oxide (EtO).
Table 12. The VenaSeal system kit contents
VenaSeal adhesive
A vial sealed with a screw-cap lid contains 5 cc of the VenaSeal adhesive (a specially formulated n-butyl-2-cyanoacrylate).
Dispenser gun
The dispenser gun consists of a pistol type, ergonomic handle with an integrated barrel and trigger. Each depression of the trigger delivers a controlled
0.10 cc (range: 0.06 cc to 0.12 cc) amount of adhesive.
Laser markings on catheter
The catheter is 5 Fr with an effective length of 91 cm, laser markings at 3 cm and at 85 cm from the tip, and high echogenic visibility.
Introducer and dilator
The introducer is 7 Fr with an effective length of 80 cm and circumferential markings in 10 mm intervals along its length for measuring retraction length
during the VenaSeal procedure.
Introducer and catheter
The dilator is 5 Fr with an effective length of 87 cm.
3 cc syringe
The 3 cc syringes are graduated Monoject™ luer lock syringes, each with a standard threaded luer lock connectora.
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Table 12. The VenaSeal system kit contents (continued)
Dispenser tip
The dispenser tips are each comprised of a stainless steel, 1.5 mm inner diameter, 3.8 cm length hypotube with a luer lock connector.
Straight floppy tip guidewire
The guidewire is a 0.035 in, 180 cm straight floppy tip guidewire.
a
Third-party brands are trademarks of their respective owners.
9 Storage
The VenaSeal system should be stored in its dispenser box carton at room temperature and humidity. The kit should only be opened, and the components should only be removed from the
carton, upon use of the system.
10 Directions for use
10.1 Recommended accessories
The VenaSeal closure system will require the use of the following commercially available components (not supplied):
• 5 Fr micro-access kit (or equivalent)
– 21 gauge guidewire insertion needle
– 0.018 in micro-access kit guidewire
– Micro-access sheath
– Micro-access dilator
• Flushing syringe
• Sterile saline
Reminder: Medtronic requires physicians to be trained on the VenaSeal system prior to independent commercial use. Serious, including fatal, consequences could result with
the use of the VenaSeal system without adequate training. Contact your Medtronic sales representative for information on training.
10.2 Preparation
Prior to use, perform a baseline ultrasound to map the incompetent vein to be treated. Use sterile technique. Use local anesthetic at the access site.
1. Review the preliminary ultrasound map of the incompetent vein to be treated. Perform a final assessment using duplex ultrasound with the subject in the supine position.
2. Under ultrasound guidance, locate the target vein for treatment and locate its most distal location.
Note: For treatment of the great saphenous vein (GSV) or anterior accessory great saphenous vein (AAGSV), locate the target vein and saphenofemoral junction (SFJ). Trace the vein
to determine a site at its distal end for access. The following instructions are specific to treating the GSV.
Note: For treatment of the small saphenous vein (SSV), locate the target vein and saphenopopliteal junction (SPJ). Trace the vein to determine a site at its distal end for access.
3. Prepare and drape the selected access site as required per standard procedures.
4. Administer local anesthetic at the selected access site.
10.3 Access
1. Under ultrasound guidance, access the target vein with a 21 gauge guidewire insertion needle from a 5 Fr micro-access kit or equivalent using the Seldinger technique.
2. Advance a 0.018 in micro-access kit guidewire into the vein and confirm venous access by using ultrasound.
3. Remove the guidewire insertion needle and advance the micro-access sheath and dilator assembly over the micro-access kit guidewire and into the vein.
4. Remove the micro-access kit guidewire and micro-access dilator.
5. Advance the supplied 0.035 in, 180 cm straight floppy tip guidewire through the micro-access sheath and into the lumen of the vein.
6. Under real-time ultrasound, position the supplied guidewire just caudal to the saphenofemoral junction (SFJ).
7. Confirm supplied guidewire positioning using ultrasound. After confirmation, remove the micro-access sheath and advance the 7 Fr introducer and dilator assembly from the VenaSeal
closure system over the guidewire to the SFJ.
8. Remove the supplied guidewire and dilator.
9. Flush the introducer through the luer injection port with sterile saline using a flushing syringe. Leave the syringe in place.
10. Under real-time ultrasound guidance, position the introducer tip 5 cm (range: 4 cm to 6 cm) caudal from the SFJ.
10.4 Assembly
1. Attach a dispenser tip to the 3 cc syringe from the VenaSeal system.
2. Use the dispenser tip and 3 cc syringe combination to extract the VenaSeal adhesive from its vial into the 3 cc syringe. Purge visible air from the 3 cc syringe. See the reference chart
(Table 13) for total amount of adhesive delivered as a function of planned treatment length.
3. Once the 3 cc syringe is filled with the VenaSeal adhesive, remove the dispenser tip and connect the 3 cc syringe to the 5 Fr catheter.
4. Lock the 3 cc syringe attached to the catheter into place within the dispenser gun. Use caution to avoid kinking the catheter. Figure 2 illustrates the assembly of the VenaSeal system. Figure 2. Illustration of the dispenser gun, 3 cc syringe, and catheter assembly
1 Dispenser gun
2 Trigger
5. Prime the catheter by pulling the trigger on the dispenser gun to advance the VenaSeal adhesive to within 3 cm (range: 2 cm to 4 cm) of the distal catheter tip. The distal laser mark denotes
3 cm from the catheter tip. Do not advance the adhesive all the way to the catheter tip during priming.
6. Remove the saline-filled flushing syringe from the introducer.
7. Insert the primed catheter into the introducer and advance until the proximal laser mark on the catheter is at the hub of the introducer. Use caution to avoid kinking the catheter.
3 3 cc syringe
4 Catheter
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8. Pull the introducer back caudal another 5 cm. Advance the catheter cephalad and lock the introducer to the catheter with the spin-lock mechanism. This action will expose the catheter
3 cm
tip, positioning it 5 cm (range: 4 cm to 6 cm) caudal to the SFJ. Verify that the catheter tip is 5 cm from the SFJ using ultrasound.
10.5 Procedure
10.5.1 Initial delivery of the adhesive
1. Using a transverse ultrasound plane, position the ultrasound transducer just cephalad (2 cm to 3 cm) to the catheter tip and apply adequate pressure to compress the GSV near the SFJ
as depicted in Figure 3.
Figure 3. Ultrasound transducer position for initial injection of the VenaSeal adhesive
2. While applying compression with the ultrasound transducer, deliver an aliquot of 0.10 cc (range: 0.06 cc to 0.12 cc) of the VenaSeal adhesive in the vein by depressing the trigger of the
dispenser gun once and holding it down for 3 seconds to completely inject the 0.10 cc of the VenaSeal adhesive. Immediately pull back 1 cm and deliver another aliquot of 0.10 cc of the
VenaSeal adhesive in the vein with an additional trigger pull, again holding down the dispenser gun trigger for 3 seconds after depressing the trigger.
3. Following this second injection, immediately (within 3 seconds) pull back the introducer and catheter assembly 3 cm, holding the transverse compression with the ultrasound transducer
for a minimum of 3 minutes. During the compression time, use a free hand caudal to the transducer to add light compression as depicted in Figure 4.
Figure 4. Pressure application in the VenaSeal system procedure
10.5.2 Subsequent delivery of the adhesive
The remaining length of vein that requires treatment can be treated with any combination of 3 cm, 6 cm, or 9 cm segments as described in the following procedure.
1. Locate the catheter tip under ultrasound guidance.
2. Apply compression on the vein caudal to the previous injection and cephalad to the catheter tip with the ultrasound transducer in a transverse plane.
3. Deliver an aliquot of 0.10 cc (range: 0.06 cc to 0.12 cc) of the VenaSeal adhesive in the vein by pulling the trigger of the dispenser gun once and holding the trigger for 3 seconds.
4. Following the injection, immediately (within 3 seconds) pull back the introducer and catheter assembly 3 cm. See Figure 5.
Note: To treat a 6 cm segment before compression, repeat steps 3 and 4 once to dispense 2 aliquots of adhesive. See Figure 6.
Note: To treat a 9 cm segment before compression, repeat steps 3 and 4 twice to dispense 3 aliquots of adhesive. See Figure 7.
Note: The treating physician should use professional judgement to determine the exact application, considering the remaining length of vein to be treated, anatomical considerations (for
example, tributaries, perforators, locations of focal dilation), and the individual patient situation.
5. While maintaining transverse compression with the ultrasound transducer, use a free hand caudal to the transducer to add light compression to the entire segment treated in Step 3 and
Step 4 for a minimum of 30 seconds. Refer to Figure 5, Figure 6, or Figure 7 depending on the length of segment being compressed.
Figure 5. Treatment of 3 cm segment
1 Delivery of adhesive and pullback
2 Thirty seconds of compression
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Figure 6. Treatment of 6 cm segment
3 cm
3 cm
3 cm
3 cm
3 cm
1 Delivery of 2 aliquots of adhesive with pullback
2 Thirty seconds of compression
Figure 7. Treatment of 9 cm segment
1 Delivery of 3 aliquots of adhesive with pullback
2 Thirty seconds of compression
6. Repeat Step 1 to Step 5 to treat the entire length of the target vein segment to a point where the 5 cm laser mark of the introducer is visible outside of the access site. Injections should
all be located within the target vein. The introducer should also remain within the target vein.
Note: Additional injections in the same location can be given during treatment at the site of tributaries or focal dilatation.
7. After the 30 seconds of compression associated with the final injection within the target vein, unlock the spin-lock mechanism of the catheter from the introducer. Maintain the introducer
position within the target vessel.
8. While holding the introducer stationary, recapture the catheter by retracting it through the introducer until the catheter’s proximal laser mark is visible 1 cm to 5 cm outside of the introducer
hub.
9. Remove the introducer and catheter together. Apply hand pressure as long as necessary to achieve hemostasis at the access site.
10. Confirm vein closure along the treated segment by using ultrasound.
10.6 If the primed catheter needs to be withdrawn from the introducer prior to completion, take the following steps:
1. If the adhesive has not been delivered through the distal end of the catheter (Section 10.4, Step 6 to Section 10.5.1, Step 1), perform the following steps:
a. Ensure that no adhesive has been delivered from the catheter tip.
b. If no adhesive has been delivered from the catheter tip, unscrew the catheter and withdraw it.
2. If the adhesive has been injected through the distal end of the catheter (after Section 10.5.1, Step 1), perform the following steps:
a. Withdraw both the introducer and the catheter by following Section 10.5.2, Step 7 to Section 10.5.2, Step 9.
Note: Step 2b to Step 2i are performed outside the body.
b. Re-expose the tip of the catheter and re-lock the catheter to the introducer with the spin-lock mechanism.
c. Push the white button on top of the dispenser gun and pull back the plunger rod.
d. Unlock and release the syringe with the attached catheter from the dispenser gun.
e. Pull back gently on the syringe plunger to draw the adhesive back into the catheter.
f. The adhesive should be drawn at least 5 cm to 10 cm from the distal laser mark on the catheter.
g. Remove any residual adhesive by repeatedly wiping the tip of the catheter with sterile gauze.
h. After confirming that the tip is cleaned of adhesive, unscrew the catheter from the introducer and withdraw the catheter.
i. Flush the introducer sheath with sterile saline.
3. To reintroduce the catheter into the introducer, follow Section 10.3, Step 6 to Section 10.5.1, Step 1.
10.7 Total amounts of VenaSeal adhesive expected for use in vein treatments
The amount of adhesive delivered is related to length of the target GSV. The VenaSeal system Instructions for Use describe the application of 0.10 cc of the VenaSeal adhesive every 3 cm
in the target vein. In addition, the first delivery consists of 0.20 cc. Table 13 shows a calculation of the total expected amount of adhesive delivered as a function of target treatment length.
Additional injections could be administered at sites of dilatation and junctions with tributaries. The exact application procedure and dosage is to be determined by the physician.
Total amount of adhesive delivered as a function of planned treatment length (for reference only)
Table 13.
Planned treatment length (cm) Initial delivery (cc) Subsequent number of deliveries Total amount of adhesive (cc)
10 0.2 3 0.5
15 0.2 5 0.7
13
Table 13. Total amount of adhesive delivered as a function of planned treatment length (for reference only) (continued)
Planned treatment length (cm) Initial delivery (cc) Subsequent number of deliveries Total amount of adhesive (cc)
20 0.2 7 0.9
25 0.2 8 1
30 0.2 10 1.2
35 0.2 12 1.4
40 0.2 13 1.5
45 0.2 15 1.7
50 0.2 17 1.9
55 0.2 18 2
60 0.2 20 2.2
65 0.2 22 2.4
70 0.2 23 2.5
75 0.2 25 2.7
80 0.2 26 2.8
85 0.2 28 3.0
90 0.2 30 3.2
11 Disposal
Dispose of the VenaSeal system in accordance with applicable laws, regulations, and hospital procedures regarding biohazardous medical devices.
12 Disclaimer of warranty
The warnings contained in the product labeling provide more detailed information and are considered an integral part of this disclaimer of warranty. Although the product
has been manufactured under carefully controlled conditions, Medtronic has no control over the conditions under which this product is used. Medtronic, therefore, disclaims
all warranties, both express and implied, with respect to the product, including, but not limited to, any implied warranty of merchantability or fitness for a particular purpose.
Medtronic 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.
14
Medtronic, Inc.
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Minneapolis, MN 55432
USA
www.medtronic.com
+1 763 514 4000
LifeLine Technical Support, 24-hour consultation service:
1 877 526 7890
© 2020 Medtronic
M002482C001 A
2020-01-31
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