Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease

Study Overview
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Brief Summary
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The objective of this Study is to evaluate the safety and efficacy of the IN.PACT Admiral® drug coated PTA balloon, utilized for the dilatation of the narrowed sections of the artery, as compared to other standard (non drug coated) PTA balloons. The IN.PACT Admiral, besides the mechanical dilatation effect typical of all PTA balloons, releases a drug (paclitaxel) from the balloon surface into the vessel walls. This drug absorption is intended to limit the chances and the entity of artery re-narrowing over time.

Detailed Description
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The efficacy of the IN.PACT Admiral balloon will be evaluated by assessing the primary patency rate of the treated arteries in the thighs of all patients included in the Study. Primary patency is a measure of the durability up to 1 year of the free lumen in the artery as restored during the procedure and is based on: the need for re-dilatation of the previously treated vessel segment an ultrasound examination The safety of the IN.PACT Admiral will be assessed by evaluating the incidence of deaths, amputations and re-dilatation of the pre-treated arteries in all patients included in the Study. 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 Admiral(TM) Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease

Conditions
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Peripheral Arterial Disease (PAD)

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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General Inclusion Criteria: Age ≥18 years and ≤85 years Patient or patient's legal representative is informed of the nature of the study, agrees to participate and has signed an EC approved consent form Angiographic Inclusion Criteria: - Target vessel is the superficial femoral artery and/or proximal popliteal artery (above the knee) General Exclusion Criteria: Patient unwilling or unlikely to comply with follow-up schedule Stroke or STEMI within 3 months prior enrolment Angiographic Exclusion Criteria: - Acute or sub-acute thrombus in the target vessel

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: None (Open Label)


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>* balloon dilatation and provisional stenting with IN.PACT DCB<br>|
| Active Comparator: Standard PTA<br>Standard Percutaneous Transluminal Angioplasty (PTA) Balloon: Balloon Angioplasty | Device: PTA Balloon: Balloon Angioplasty<br>* balloon dilatation and provisional stenting with standard non-coated PTA balloon<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 revascularization (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 Events (MAE) Composite | Major Adverse Events (MAE) composite defined as all-cause death, clinically-driven target vessel revascularization (CD-TVR), 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. Rutherford classification is a clinical staging system that is used to describe peripheral arterial disease. | 12 month | 
| Secondary Sustained Clinical Improvement | Freedom from target limb amputation and increase in Rutherford class. | 12 month | 
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4). | Duplex ultrasound measurement that measures the peak systolic velocity of blood (cm/sec) within a lesion divided by the peak velocity of blood (cm/sec) proximal to the lesion. | 12 month | 
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio >3.4). |  | 12 month | 
| Change From Baseline in Quality of Life Assessment by EuroQol Group 5-Dimension Self Report Questionnaire (EQ5D) at Month 12 | 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'. | Baseline to 12 month | 
| Change From Baseline in Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) at 12 Months | 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 obtainment of ≤30% residual stenosis by visual estimate (with or without stenting) | Day 1 | 
| Clinical Success | Clinical success is defined as procedural success without procedural complications (death, stroke, 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 |