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

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

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

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.

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.

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.

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.

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

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.

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.

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.

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'.

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).

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).

Procedural success is defined as obtainment of ≤30% residual stenosis by visual estimate (with or without stenting)

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.

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

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Schneider PA, Laird JR, Doros G, Gao Q, Ansel G, Brodmann M, Micari A, Shishehbor MH, Tepe G, Zeller T. Mortality Not Correlated With Paclitaxel Exposure: An Independent Patient-Level Meta-Analysis of a Drug-Coated Balloon. J Am Coll Cardiol. 2019 May 28;73(20):2550-2563. doi: 10.1016/j.jacc.2019.01.013. Epub 2019 Jan 25. Erratum In: J Am Coll Cardiol. 2019 Feb 28;:

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