IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery (SFA) and Proximal Popliteal Artery (PPA)

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) in comparison to any standard balloon for treatment of peripheral arterial disease (PAD) in the superficial femoral artery and proximal popliteal artery.

Detailed Description
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The IN.PACT SFA Trial enrolled in 2 phases: IN.PACT SFA I and IN.PACT SFA II. The 150-patient IN.PACT SFA I phase is intended to support the second phase IN.PACT SFA II IDE trial with congruent design and protocol. Aggregate data from the two phases is intended to provide statistical power for the 12-month primary safety and effectiveness endpoints.

Official Title
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Randomized Trial of IN.PACT (Paclitaxel) Admiral Drug-Coated Balloon (DCB) vs. Standard Percutaneous Transluminal Angioplasty (PTA) for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA)

Conditions
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Femoral Artery Occlusion, Popliteal Artery Occlusion, Femoral Artery Stenosis, Popliteal Artery Stenosis

Intervention / Treatment
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* Device: Drug-Coated Balloon (DCB)
* Device: PTA Balloon: Balloon Angioplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: > or equal to 18 years and < or equal to 85 years Documented ischemia with Rutherford classification 2, 3, or 4 Target lesion in the SFA and/or PPA Angiographic evidence that target lesion consists of a single de novo or non-stented restenotic lesion or is a combination lesion that meets the following criteria: 70 - 99% occlusion by visual estimate with lesion length > or equal to 4 cm and < or equal to 18 cm 100% occlusion by visual estimate with lesion length < or equal to 10 cm Combination lesions must have a total lesion length of > or equal to 4 cm and < or equal to 18 cm with an occluded segment that is < or equal to 10 cm (by visual estimate) Target vessel diameter > or equal to 4 mm and < or equal to 7 mm Angiographic evidence of adequate distal run-off to the ankle Able to walk without assistive devices Exclusion Criteria: Stroke or heart attack within 3 months prior to enrollment Enrolled in another investigational drug, device or biologic study Any surgical procedure or intervention performed within 30 days prior to or post index procedure SFA or PPA disease in the opposite leg that requires treatment at the index procedure Failure to successfully cross the target lesion Angiographic evidence of severe calcification Target lesion requires treatment with alternative therapies such as stenting, laser, atherectomy, cryoplasty, brachytherapy, re-entry devices) Known allergies or sensitivity to heparin, aspirin, other anticoagulant/antiplatelet therapies, paclitaxel or contrast media that cannot be adequately pre-treated prior to index procedure Chronic kidney disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug-Coated Balloon (DCB)<br>IN.PACT Admiral: Balloon Angioplasty | Device: Drug-Coated Balloon (DCB)<br>* Subjects will be randomized 2:1 to the IN.PACT Admiral Drug-Coated Balloon (DCB) Arm or to the standard angioplasty balloon Arm<br>|
| Active Comparator: Standard PTA<br>Standard Percutaneous Balloon Angioplasty (PTA) Balloon: Balloon Angioplasty | Device: PTA Balloon: Balloon Angioplasty<br>* Subjects will be randomized 2:1 to the IN.PACT Admiral Drug-Coated Balloon (DCB) Arm or to the standard angioplasty balloon Arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency | Primary patency is defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or restenosis as determined by duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) ≤2.4. | 12 month | 
| Primary Safety Composite | Primary safety composite is defined as freedom from death through 30 days or target limb major amputation or clinically-driven target vessel revascularization (CD-TVR) within 12 months post index procedure. | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Event (MAE) Composite | Major Adverse Event (MAE) composite is defined as all cause death, clinically-driven target vessel revascularization, major target limb amputation, thrombosis at the target lesion site. | 12 month | 
| All-cause Death |  | 12 month | 
| Target Vessel Revascularization (TVR) |  | 12 month | 
| Target Lesion Revascularization (TLR) |  | 12 month | 
| Time to First Clinically Driven Target Lesion Revascularization (CD-TLR) | Clinically-driven target lesion revascularization (CD-TLR) is defined as any re-intervention within the target lesion due to symptoms or drop of ankle brachial index (ABI) of ≥20% or >0.15 when compared to post procedure baseline. | 12 month | 
| Major Target Limb Amputation |  | 12 month | 
| Thrombosis at the Target Lesion |  | 12 month | 
| Primary Sustained Clinical Improvement | Freedom from target limb amputation, target vessel revascularization (TVR), and increase in Rutherford class. | 12 month | 
| Secondary Sustained Clinical Improvement | Freedom from target amputation and increase in Rutherford class. | 12 month | 
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4) |  | 12 month | 
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >3.4) |  | 12 month | 
| Quality of Life Assessment by EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) | Quality of life assessment by EQ5D at 1 year compared to baseline. EQ5D is a standardised measure of health status and economic appraisal. The EQ5D consists of the EQ5D descriptive system which comprises the following variables for the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: (1) no problems, (2) some problems, (3) extreme problems. A complex algorithm that took individual dimensions and generated an overall score was used. EQ5D health state is used in the algorithm to calculate an overall score where - 0.109 = 'worst possible outcome' and 1.000 = 'best possible outcome'. | 12 month | 
| Change in Walking Distance as Assessed by Six Minute Walk Test (6MWT) | Change from baseline in walking distance by Six Minute Walk Test (6MWT) at 12 month. | From baseline to 12 month | 
| Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) | Walking capacity assessment by WIQ at 1 year compared to baseline. WIQ is a quality of life questionnaire that was specifically designed to assess the degree of impairment experienced by patients with claudication. Clinical outcomes were assessed by patients responses to question 1A. Question 1A is specific for calf or buttocks claudication and is used to create a summary score for analysis. Question 1A is expressed on a scale of 0% (unable to perform because of severe claudication) to 100% (no impairment). | 12 month | 
| Device Success | Device success is defined as successful delivery, balloon inflation and deflation and retrieval of the intact study device without burst below rated burst pressure (RBP). | Day 1 | 
| Procedural Success | Procedural success is defined as residual stenosis of ≤50% (non-stented subjects) or ≤30% (stented subjects) by core lab assessment. | Day 1 | 
| Clinical Success | Clinical success is defined as procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or Target vessel revascularization (TVR)) prior to discharge. | Day 1 | 
| Days of Hospitalization Due to the Index Lesion | Days of hospitalization from procedure through 12 month. | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-Coated Angioplasty Balloon, Drug Coated Angioplasty Balloon, Peripheral Artery Disease, Experimental, Percutaneous Transluminal Angioplasty (PTA)