Medtronic IAV04012004P Instructions for Use
IN.PACT™ AV
Paclitaxel-coated PTA Balloon Catheter
Instructions for Use
Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.
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company.
Explanation of symbols on package labeling
Sterilized using ethylene oxide
Catalog number
Lot number
Manufacturer
Manufactured in
Use-by date
Quantity
Consult instructions for use at this website: www.medtronic.com/manuals
Do not reuse
Do not resterilize
Keep away from sunlight
Keep dry
Do not use if package is damaged
Outer diameter
Temperature limit
Nonpyrogenic
Over the wire
Nominal pressure
Rated burst pressure
Do not exceed rated burst pressure
Inflation pressure
Balloon diameter
Minimum sheath inner diameter
Maximum guidewire diameter
Balloon length
Usable catheter length
1
IN.PACT™ AV
Paclitaxel-coated PTA Balloon Catheter
Table of contents
1. Product Name ......................................................................................................................................................................................................................................................... 2
2. Product Description ............................................................................................................................................................................................................................................... 2
3. Indications for Use ................................................................................................................................................................................................................................................. 4
4. Contraindications ................................................................................................................................................................................................................................................... 4
5. Warnings ................................................................................................................................................................................................................................................................. 4
6. Precautions ............................................................................................................................................................................................................................................................. 4
7. Use in Special Populations .................................................................................................................................................................................................................................... 5
8. Drug Information ..................................................................................................................................................................................................................................................... 5
9. Potential Adverse Effects ...................................................................................................................................................................................................................................... 6
10. Patient Counseling Information ............................................................................................................................................................................................................................ 6
11. Summary of Clinical Study .................................................................................................................................................................................................................................... 6
12. How Supplied ........................................................................................................................................................................................................................................................ 18
13. Instructions for Use .............................................................................................................................................................................................................................................. 18
14. DISCLAIMER OF WARRANTY .............................................................................................................................................................................................................................. 21
1. Product Name
IN.PACT™ AV paclitaxel-coated percutaneous transluminal angioplasty (PTA) balloon catheter
2. Product Description
The IN.PACT AV paclitaxel-coated PTA balloon catheter, hereafter referred to as the IN.PACT AV DCB, is an over-the-wire (OTW) balloon catheter with a drug-coated balloon (DCB)
at the distal tip. The drug component, referred to as the FreePac™ coating, consists of the drug paclitaxel and the excipient urea. The device component physically dilates the vessel
lumen by PTA, and the drug is intended to reduce the proliferative response that is associated with restenosis. Product Component Description (Table 1) summarizes the
characteristics of the device.
Table 1. Product Component Description
Balloon Diameter
4.0 mm X X X X
5.0 mm X X X X
Available Balloon Diameters
(mm) and Lengths (mm)
Balloon Coating (Drug Component)
Catheter Design Over-the-Wire (OTW)
Usable Catheter Lengths 40 cm, 80 cm and 130 cm
Balloon Inflation Pressure
Minimum Introducer Sheath
Compatibility
Guidewire Compatibility The catheter is compatible with a guidewire diameter of 0.035 in (0.89 mm).
2.1. Device Component Description
The balloon catheter consists of a proximal hub, dual-lumen shaft, and a distal dilatation balloon. The central lumen extends to the distal tip and is used to pass the catheter over a
guidewire with a diameter of 0.035 in (0.89 mm). The balloon-inflation lumen is used to inflate and deflate the balloon with a mixture of contrast medium and saline solution. Two
radiopaque platinum-iridium markers indicate the working length of the balloon to position the balloon across the target lesion during fluoroscopy. See IN.PACT AV Paclitaxel-coated
PTA Balloon Catheter (Figure 1).
Note: “---” indicates sizes not offered; “X” indicates sizes offered
Paclitaxel (Active Pharmaceutical Ingredient) and Urea (excipient)
6.0 mm X X X X
7.0 mm X X X ---
8.0 mm X X X ---
9.0 mm X X X ---
10.0 mm X --- --- ---
12.0 mm X --- --- ---
Balloon Diameter Nominal Pressure Rated Burst Pressure
4.0 mm
5.0 mm
6.0 mm
7.0 mm
8.0 mm
9.0 mm
10.0 mm
12.0 mm
Balloon Diameter Max. Crossing Profile Introducer Sheath
4.0 mm 5.6 F (1.88 mm) 5 F
5.0 mm 6.0 F (2.00 mm)
6.0 mm 6.3 F (2.10 mm)
7.0 mm
8.0 mm
9.0 mm
10.0 mm
12.0 mm 9.0 F (3.00 mm) 9 F
40 mm 60 mm 80 mm 120 mm
Balloon Length
1419 kPa / 14 atm
811 kPa / 8 atm
1013 kPa / 10 atm
608 kPa / 6 atm 912 kPa / 9 atm
6 F
7.0 F (2.33 mm) 7 F
2 Instructions for Use English
8
77
2
5
4
1
6
3
Figure 1. IN.PACT AV Paclitaxel-coated PTA Balloon Catheter
1
2
12
11
10
9
8
7
6
5
4
3
13
14
20
19
18
17
16
15
3’
2’
1’
1. Guidewire port
2. Hub
3. Inflation port
4. Strain relief
5. Shaft
6. Usable catheter length
7. Radiopaque marker
8. Drug-coated balloon
2.2. Drug Component Description
The FreePac™ drug coating on the balloon of the IN.PACT AV DCB consists of the drug paclitaxel and the excipient urea. The balloon surface has a nominal paclitaxel dose density
of 3.5 μg/mm2.
2.2.1. Paclitaxel
The active pharmaceutical ingredient in the IN.PACT AV DCB is paclitaxel. The principal mechanism by which paclitaxel inhibits neointimal growth is through the stabilization of
microtubules by preventing their depolymerization during the final G2/M phase of cell division.
The CAS Registry number of paclitaxel is 33069-62-4. The chemical name of paclitaxel is:
Benzenepropanoic acid, ß-(benzoylamino)-α-hydroxy-,6,12b-bis(acetyloxy)-12-(benzoyloxy) -2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dhydroxy-4a,8,13,13-tetramethyl-5-
oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]-oxet-9-ylester,[2aR-[2aα,4β,4aβ,6β,9α(αR, βS),11α,12α,12aα,12bα]]
See Chemical Structure of Paclitaxel (Figure 2) below.
Figure 2. Chemical Structure of Paclitaxel
Paclitaxel is a diterpenoid with a characteristic taxane skeleton of 20 carbon atoms, a molecular weight of 853.91 g/mol, and a molecular formula of C47H51NO14. It is a white powder,
has extremely low water solubility, is highly lipophilic, and is freely soluble in methanol, ethanol, chloroform, ethyl acetate, and dimethyl sulfoxide.
2.2.2. Urea
The coating utilizes the inactive ingredient urea as an excipient to facilitate the release and transfer of paclitaxel into the vessel wall. See Chemical Structure of Urea (Figure 3) below.
Figure 3. Chemical Structure of Urea
2.2.3. Product Matrix and Paclitaxel Content
Code (40 cm Usa-
Product
ble Catheter Length)
IAV 040 040 04P IAV 040 040 08P IAV 040 040 13P 4.0 40 1969
IAV 040 060 04P IAV 040 060 08P IAV 040 060 13P 4.0 60 2848
IAV 040 080 04P IAV 040 080 08P IAV 040 080 13P 4.0 80 3728
IAV 040 120 04P IAV 040 120 08P IAV 040 120 13P 4.0 120 5487
IAV 050 040 04P IAV 050 040 08P IAV 050 040 13P 5.0 40 2553
IAV 050 060 04P IAV 050 060 08P IAV 050 060 13P 5.0 60 3653
IAV 050 080 04P IAV 050 080 08P IAV 050 080 13P 5.0 80 4752
Product Code (80 cm Usa-
ble Catheter Length)
Table 2. Product Matrix and Paclitaxel Content
Product Code (130 cm
Usable Catheter Length)
Nominal Balloon Diameter
(mm)
Nominal Balloon Length
(mm)
Nominal Paclitaxel
Content (μg)
Instructions for Use English 3
Product Code (40 cm Usa-
ble Catheter Length)
IAV 050 120 04P IAV 050 120 08P IAV 050 120 13P 5.0 120 6951
IAV 060 040 04P IAV 060 040 08P IAV 060 040 13P 6.0 40 3170
IAV 060 060 04P IAV 060 060 08P IAV 060 060 13P 6.0 60 4489
IAV 060 080 04P IAV 060 080 08P IAV 060 080 13P 6.0 80 5809
IAV 060 120 04P IAV 060 120 08P IAV 060 120 13P 6.0 120 8448
IAV 070 040 04P IAV 070 040 08P IAV 070 040 13P 7.0 40 3819
IAV 070 060 04P IAV 070 060 08P IAV 070 060 13P 7.0 60 5358
IAV 070 080 04P IAV 070 080 08P IAV 070 080 13P 7.0 80 6897
IAV 080 040 04P IAV 080 040 08P IAV 080 040 13P 8.0 40 4494
IAV 080 060 04P IAV 080 060 08P IAV 080 060 13P 8.0 60 6253
IAV 080 080 04P IAV 080 080 08P IAV 080 080 13P 8.0 80 8012
IAV 090 040 04P IAV 090 040 08P IAV 090 040 13P 9.0 40 5204
IAV 090 060 04P IAV 090 060 08P IAV 090 060 13P 9.0 60 7183
IAV 090 080 04P IAV 090 080 08P IAV 090 080 13P 9.0 80 9162
IAV 100 040 04P IAV 100 040 08P IAV 100 040 13P 10.0 40 5943
IAV 120 040 04P IAV 120 040 08P IAV 120 040 13P 12.0 40 7522
Product Code (80 cm Usa-
ble Catheter Length)
Product Code (130 cm
Usable Catheter Length)
Nominal Balloon Diameter
(mm)
Nominal Balloon Length
(mm)
Nominal Paclitaxel
Content (μg)
3. Indications for Use
The IN.PACT AV paclitaxel-coated PTA balloon catheter is indicated for percutaneous transluminal angioplasty, after appropriate vessel preparation, for the treatment of obstructive
lesions up to 100 mm in length in the native arteriovenous dialysis fistulae with reference vessel diameters of 4 to 12 mm.
4. Contraindications
The IN.PACT AV DCB is contraindicated for use in the following anatomy and patient types:
■
Coronary arteries, renal arteries, and supra-aortic/cerebrovascular arteries
■
Patients who cannot receive recommended antiplatelet and/or anticoagulant therapy
■
Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the delivery system
■
Patients with known allergies or sensitivities to paclitaxel
■
Women who are breastfeeding, pregnant, or are intending to become pregnant, or men intending to father children. It is unknown whether paclitaxel will be excreted in human milk
and whether there is a potential for adverse reaction in nursing infants from paclitaxel exposure
5. Warnings
■
A signal for increased risk of late mortality has been identified following the use of paclitaxel-coated balloons and paclitaxel-eluting stents for femoropopliteal arterial
disease beginning approximately 2-3 years post-treatment compared with the use of non-drug coated devices. There is uncertainty regarding the magnitude and
mechanism for the increased late mortality risk, including the impact of repeat paclitaxel-coated device exposure. Inadequate information is available to evaluate the
potential mortality risk associated with the use of paclitaxel-coated devices for the treatment of other diseases/conditions, including this device indicated for use in
arteriovenous dialysis fistulae. Physicians should discuss this late mortality signal and the benefits and risks of available treatment options for their specific
disease/condition with their patients. See Section 11.1 for further information.
■
Use the product prior to the Use-by date specified on the package.
■
Contents are supplied sterile. Do not use the product if the inner packaging is damaged or opened.
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Do not use air or any gaseous medium to inflate the balloon. Use only the recommended inflation medium (equal parts contrast medium and saline solution).
■
Do not move the guidewire during inflation of the IN.PACT AV DCB.
■
Do not exceed the rated burst pressure (RBP). The RBP is based on the results of in vitro testing. Use of pressures higher than RBP may result in a ruptured balloon with possible
intimal damage and dissection. Refer to Product Component Description (Table 1) for RBP information.
■
The safety of using multiple IN.PACT AV DCBs with a total drug dosage exceeding 15,105 μg paclitaxel has not been evaluated clinically.
6. Precautions
6.1. General Precautions
■
This product should only be used by physicians trained in percutaneous transluminal angioplasty (PTA).
■
Assess risks and benefits before treating patients with a history of severe reaction to or inability to tolerate contrast agents. Identify allergic reactions to contrast media and
antiplatelet therapy before treatment and consider alternatives for appropriate management prior to the procedure.
■
Administer appropriate drug therapy to the patient according to standard protocols for PTA before insertion of the dilatation catheter.
■
Take precautions to prevent or reduce clotting when any catheter is used. Flush and rinse all products entering the vascular system with heparinized normal saline or a similar
solution. For the IN.PACT AV DCB catheter, flush the guidewire lumen through the guidewire port with heparinized normal saline until the fluid exits the distal tip. Do not rinse or
wipe the IN.PACT AV DCB catheter.
■
Prior to the procedure, inspect the product to verify that the product is intact.
■
Handle the product with caution to avoid any damage to the balloon coating or folded balloon.
■
This product is not intended for the expansion or delivery of a stent or graft.
■
Do not use the IN.PACT AV DCB for pre-dilatation or for post-dilatation.
■
This product is designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing, or resterilization may compromise the structural
integrity of the device and/or create a risk of contamination of the device, which could result in patient injury, illness, or death.
■
Do not expose the product to organic solvents such as alcohol.
■
To reduce the potential for vessel damage, the inflated diameter of the balloon should approximately match the inner diameter of the vessel just distal to the lesion.
■
The use of this product carries the risks associated with percutaneous transluminal angioplasty, including thrombosis, vascular complications, and/or bleeding events.
6.2. Pre-procedure and Post-procedure Medication Regimen
It is recommended that single antiplatelet therapy (e.g. aspirin, clopidogrel, ticlopidine, or prasugrel), at a minimum, should be administered before the procedure and for at least
4 weeks after the procedure. Prolonged antiplatelet therapy can be given at the discretion of the physician.
6.3. Use of Multiple Balloons
The extent of the patient’s exposure to the drug coating is directly related to the number of balloons used. Refer to Using Multiple IN.PACT AV DCBs (Section 13.9) and Product
Matrix and Paclitaxel Content (Table 2) for details regarding the use of multiple balloons and a product matrix containing the nominal paclitaxel content for each device size,
respectively.
6.4. Use in Conjunction with Other Procedures
The safety and effectiveness of the IN.PACT AV DCB used in conjunction with other drug-eluting stents or drug-coated balloons in the same procedure has not been evaluated.
6.5. Drug Interaction
Formal drug interaction studies have not been conducted with the IN.PACT AV DCB. In the clinical pharmacokinetic (PK) sub-study of the IN.PACT SFA Trial, systemic levels of
paclitaxel following treatment were low and cleared rapidly, reducing possible impact of drug-drug interactions due to concomitant medications. Consideration for both systemic and
4 Instructions for Use English
local drug interactions should be given when deciding to use IN.PACT AV DCB(s) in a patient who is taking a drug with known interactions to paclitaxel or when deciding to initiate
therapy with such a drug in a patient who has recently been treated with IN.PACT AV DCB(s). Please refer to Drug Information (Section 8).
6.6. Balloon Handling and Preparation Precautions
■
Do not remove the device from the pouch until it is needed for immediate use.
■
Handle the device with caution to avoid any damage to the balloon coating or folded balloon.
■
Keep the protective sheath in place when purging the balloon catheter of air bubbles.
■
Carefully remove and discard the balloon’s protective sheath.
■
Do not use the protective sheath as an introduction aid or a rewrapping tool.
■
Do not apply positive pressure to the balloon during preparation.
6.7. Balloon Placement Precautions
■
Do not move the guidewire during inflation of the balloon.
■
Do not manipulate the IN.PACT AV DCB while inflated.
■
Catheter applications vary. Select the technique on the basis of the patient’s condition and the experience of the physician.
■
Introducer sheaths used must have lumen sizes that are suitable to accommodate the IN.PACT AV DCB. See Product Component Description (Table 1) for the introducer sheath
compatibility and crossing profile of each device size.
■
If resistance occurs during manipulation, ascertain the cause via fluoroscopy, road mapping, or digital subtraction angiography (DSA) before moving the IN.PACT AV DCB
backward or forward.
■
Do not manipulate the IN.PACT AV DCB without sufficient fluoroscopy.
■
Use a pressure-monitoring device to prevent over-pressurization. Refer to Product Component Description (Table 1) for RBP information.
■
To ensure full coverage of the entire lesion, the balloon diameter must match the inner diameter of the reference vessel distal to the lesion and the balloon length must exceed the
lesion length by approximately 1 cm on both ends. When using multiple balloons, do so only as described in Using Multiple IN.PACT AV DCBs (Section 13.9).
■
Never advance the IN.PACT AV DCB without the guidewire extending from the tip.
■
Balloon inflation must be for at least 180 seconds. Adequate drug transfer occurs in the first 60 seconds of inflation. The additional 120 seconds is intended solely for mechanical
dilatation purposes for optimal PTA.
■
Appropriate vessel preparation is required prior to use of the IN.PACT AV DCB. Vessel preparation of the target lesion using high-pressure PTA for pre-dilatation was studied in
the IN.PACT AV Access clinical study. Other methods of vessel preparation, such as atherectomy, have not been studied clinically with IN.PACT AV DCB.
■
Appropriate vessel preparation as determined by the physician to achieve residual stenosis of ≤ 30% is required prior to use of the IN.PACT AV DCB.
6.8. Balloon Catheter Removal Precautions
■
Prior to withdrawing the balloon catheter from the lesion, completely deflate the balloon under vacuum.
■
Center the IN.PACT AV DCB relative to the introducer sheath when withdrawing, and use caution when removing the IN.PACT AV DCB.
■
Should unusual resistance be felt at any time when withdrawing the balloon catheter back into the introducer sheath, remove the balloon catheter and the introducer sheath as a
single unit to reduce the risk of vascular damage. This must be done under direct visualization with fluoroscopy.
■
If removal of the IN.PACT AV DCB is required prior to deployment and a repeat attempt is desired, use a new IN.PACT AV DCB.
6.9. Post-procedure Precautions
■
Administer post-procedure antiplatelet therapy as described in Pre-procedure and Post-procedure Medication Regimen (Section 6.2).
7. Use in Special Populations
7.1. Pregnancy and Lactation
The IN.PACT AV DCB is contraindicated in women who are breastfeeding, pregnant, or are intending to become pregnant, or men intending to father children. It is unknown whether
paclitaxel will be excreted in human milk and whether there is a potential adverse reaction in nursing infants from paclitaxel exposure
7.2. Gender
The outcomes are shown in Table 10. The results of an interaction analysis indicate that the treatment differences between the IN.PACT AV DCB study group and the PTA control
group are consistent between male and female subjects.
7.3. Ethnicity
Due to the nature of the global trial design, the IN.PACT AV DCB study did not include a sufficient number of patients to assess treatment differences in safety or effectiveness due to
ethnicity.
7.4. Pediatric Use
The safety and effectiveness of the IN.PACT AV DCB in pediatric patients has not been established.
7.5. Geriatric Use
The IN.PACT AV DCB study had an upper age limit of 94 years, and had predefined study subgroups of ≤ the median age of 67.0 years and > the median age of 67.0 years. Within
both subgroups, the IN.PACT AV DCB study group showed improvement on the primary effectiveness endpoints, and no statistically significant difference between treatment groups
on the primary safety endpoint. The results of an exploratory analysis indicate that the treatment differences between IN.PACT AV DCB and PTA groups are generally consistent
between 2 age groups defined by median age.
8. Drug Information
8.1. Mechanism of Action
The mechanism(s) by which the IN.PACT AV DCB affects neointimal production has not been fully established. The principal mechanism by which paclitaxel inhibits neointimal growth
is through the stabilization of microtubules by preventing their depolymerization during the final G2/M phase of cell division. Consequently, the microtubule network may not maintain
the dynamic rearrangement required for a normal mitotic process.
8.2. Pharmacokinetics
Human pharmacokinetics was investigated as a sub-study of the IN.PACT SFA Trial in 25 patients receiving 2850 μg to 16,900 μg of paclitaxel. Paclitaxel systemic exposure in the
treated subjects was low and cleared rapidly with a bi-phasic decline. The C
pharmacokinetic sub-study demonstrated low systemic exposure with rapid clearance of paclitaxel.
8.3. Metabolism
Metabolic transformation of paclitaxel occurs predominantly in the liver through cytochromes P450 2C8 (CYP2C8) and 3A4 (CYP3A4). Agents which could compete with or inhibit the
activity of the CYP2C8 and CYP3A4 isoenzymes may increase paclitaxel plasma levels. For more information on potential drug interactions, see Drug Interaction (Section 6.5).
8.4. Carcinogenicity, Genotoxicity, and Reproductive Toxicity
No long-term studies in animals have been published in peer-reviewed literature to evaluate the carcinogenic potential of paclitaxel. Paclitaxel was not mutagenic in the Ames test or
the CHO/HGPRT gene mutation assay. However, the mechanism by which paclitaxel interferes with cellular proliferation may give rise to loss of chromosomes during cell division as
a result of microtubule stabilization during cell division. Paclitaxel is an established aneugenic drug in vitro on human normal cells and will also produce a positive response in the
mouse bone marrow micronucleus assay. It has not been established that paclitaxel exerts any direct action on DNA to induce strand fragmentation
Reproductive toxicity has been previously evaluated in vivo in both rabbits and rats. When administered during rabbit fetal organogenesis, paclitaxel doses of 3.0 mg/kg/day caused
embryo- and fetotoxicity; maternal toxicity was also observed. No teratogenic effects were observed at 1.0 mg/kg/day; effects at higher doses could not be assessed due to fetal
mortality. In rats, fertility impairment was observed at doses ≥ 1.0 mg/kg/day. For comparison, the average dose of paclitaxel in the IN.PACT SFA PK Sub-study was 7454 μg, with an
average subject weight of 91 kg, for a theoretical normalized dose of 0.082 mg/kg (assuming all the paclitaxel from the coating enters the systemic circulation).
ranged from 1.0 to 35.9 ng/mL and the AUC
max
ranged from 11.4 to 128.8 hr*ng/mL. The
0-∞
Instructions for Use English 5
9. Potential Adverse Effects
Potential adverse effects which may be associated with balloon catheterization may include, but are not limited to, the following:
■
Abrupt vessel closure
■
Allergic reaction
■
Arrhythmias
■
Arterial or venous aneurysm
■
Arterial or venous thrombosis
■
Death
■
Dissection
■
Embolization
■
Hematoma
■
Hemorrhage
■
Hypotension/hypertension
■
Infection
■
Ischemia or infarction of tissue/organ
■
Loss of permanent access
■
Pain
■
Perforation or rupture of the artery or vein
■
Pseudoaneurysm
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Restenosis of the dilated vessel
■
Shock
■
Stroke
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Vessel spasms or recoil
Potential complications of peripheral balloon catheterization include, but are not limited to, the following:
■
Balloon rupture
■
Detachment of a component of the balloon and/or catheter system
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Failure of the balloon to perform as intended
■
Failure to cross the lesion
These complications may result in adverse effects.
Although systemic effects are not anticipated, potential adverse effects not captured above that may be unique to the paclitaxel drug coating include, but are not limited to, the
following:
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Allergic/immunologic reaction
■
Alopecia
■
Anemia
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Gastrointestinal symptoms
■
Hematologic dyscrasia (including leucopenia, neutropenia, thrombocytopenia)
■
Hepatic enzyme changes
■
Histologic changes in vessel wall, including inflammation, cellular damage, or necrosis
■
Myalgia/arthralgia
■
Myelosuppression
■
Peripheral neuropathy
Refer to the Physician’s Desk Reference for more information on the potential adverse effects observed with paclitaxel. There may be other potential adverse effects that are
unforeseen at this time.
10. Patient Counseling Information
Physicians should consider the following when counseling patients about this product:
■
Discuss the risks associated with percutaneous transluminal angioplasty procedures.
■
Discuss the risks associated with the IN.PACT AV DCB.
■
Discuss the risks and benefits of the treatment specific to the patient.
■
Discuss the risks of early discontinuation of the antiplatelet therapy.
■
Discuss short- and long-term post-procedure changes to the patient's lifestyle.
11. Summary of Clinical Study
11.1. Late Mortality Signal for Paclitaxel-Coated Devices
A meta-analysis of randomized controlled trials published in December 2018 by Katsanos et. al. identified an increased risk of late mortality at 2 years and beyond for paclitaxelcoated balloons and paclitaxel-eluting stents used to treat femoropopliteal arterial disease. In response to these data, FDA performed a patient-level meta-analysis of long-term
follow-up data from the pivotal premarket randomized trials of paclitaxel-coated devices used to treat femoropopliteal disease using available clinical data through May 2019. The
meta-analysis also showed a late mortality signal in study subjects treated with paclitaxel-coated devices compared to patients treated with uncoated devices. Specifically, in the
3 randomized trials with a total of 1090 patients and available 5-year data, the crude mortality rate was 19.8% (range 15.9% - 23.4%) in patients treated with paclitaxel-coated devices
compared to 12.7% (range 11.2% - 14.0%) in subjects treated with uncoated devices. The relative risk for increased mortality at 5 years was 1.57 (95% confidence interval 1.16 -
2.13), which corresponds to a 57% relative increase in mortality in patients treated with paclitaxel-coated devices. As presented at the June 2019 FDA Advisory Committee Meeting,
an independent meta-analysis of similar patient-level data provided by VIVA Physicians, a vascular medicine organization, reported similar findings with a hazard ratio of 1.38 (95%
confidence interval 1.06 - 1.80). Additional analyses have been conducted and are underway that are specifically designed to assess the relationship of mortality to paclitaxel-coated
devices.
The presence and magnitude of the late mortality risk should be interpreted with caution because of multiple limitations in the available data, including wide confidence intervals due
to a small sample size, pooling of studies of different paclitaxel-coated devices that were not intended to be combined, substantial amounts of missing study data, no clear evidence of
a paclitaxel dose effect on mortality, and no identified pathophysiologic mechanism for the late deaths.
Paclitaxel-coated balloons and stents improve blood flow to the legs and decrease the likelihood of repeat procedures to reopen blocked blood vessels compared to uncoated
devices. The benefits of paclitaxel-coated devices (e.g., reduced reinterventions) should be considered in individual patients along with potential risks (e.g., late mortality).
Inadequate information is available to evaluate the potential mortality risk associated with the use of paclitaxel-coated devices for the treatment of other diseases/conditions including
this device indicated for use in arteriovenous dialysis fistulae.
In the IN.PACT AV Access study, Kaplan Meier mortality estimates at 6 and 12 months are 5.5% [2.7%, 9.7%], and 9.4% [5.5%, 14.6%], respectively, for the IN.PACT™ AV DCB
treatment device and 2.0% [0.5%, 5.2%] and 9.6% [5.5%, 15.0%], respectively, for the standard PTA control device. Additional information regarding long-term outcomes can be
found in the following sections.
6 Instructions for Use English
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