ELUVIA™ Drug-eluting Stent Versus Zilver® PTX® Stent

Study Overview
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Brief Summary
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The primary objective of this trial is to evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 140 mm in length. Long Lesion Substudy: to evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions >140 mm and ≤ 190 mm in length.

Detailed Description
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Atherosclerosis is a systemic disease that has become increasingly recognized in the expanding elderly population as a significant cause of morbidity and mortality. Atherosclerosis in the vessels of the lower extremities can cause a variety of symptoms ranging from intermittent claudication to ischemic rest pain and critical ischemia with major tissue loss. Typically, femoropopliteal lesions have been difficult to successfully treat with endovascular therapy because the disease is often diffuse and located in an area of the body subject to significant mobility stresses such as extension, contraction, compression, elongation, flexion and torsion. The IMPERIAL trial is a global, prospective, multi-center trial. Approximately 525-535 subjects will be enrolled at up to 75 study centers worldwide. Regions participating include the United States, Canada, European Union, Japan and New Zealand. The trial consists of a prospective, multicenter, 2:1 randomized (ELUVIA vs Zilver PTX), controlled, single-blind, non-inferiority trial (RCT), a concurrent, non-blinded, non-randomized, single-arm, pharmacokinetic (PK) substudy and a concurrent, non-blinded, non-randomized, Long Lesion substudy.

Official Title
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A Randomized Trial Comparing the ELUVIA™ Drug-eluting Stent Versus Zilver® PTX® Stent for Treatment of Superficial Femoral and/or Proximal Popliteal Arteries

Conditions
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Atherosclerosis of Native Arteries of the Extremities

Intervention / Treatment
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* Device: ELUVIA (Stent Implantation)
* Device: Zilver PTX (Stent Implantation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects age 18 and older. Subject (or Legal Guardian if applicable) is willing and able to provide consent before any study-specific test or procedure is performed, signs the consent form, and agrees to attend all required follow-up visits. NOTE: For subjects less than 20 years of age enrolled at a Japanese center, the subject's legal representative, as well as the subject, must provide written informed consent. Chronic, symptomatic lower limb ischemia defined as Rutherford categories 2, 3 or 4. Stenotic, restenotic or occlusive lesion(s) located in the native SFA and/or PPA: Degree of stenosis ≥ 70% by visual angiographic assessment Vessel diameter ≥ 4 and ≤ 6 mm Total lesion length (or series of lesions) ≥ 30 mm and ≤ 140 mm (Note: Lesion segment(s) must be fully covered with one ELUVIA stent or up to two Zilver PTX stents) Long Lesion Substudy: Total lesion length (or series of lesions) >140 mm and ≤ 190 mm (Note: Lesion segment(s) will require overlapping of two ELUVIA stents). For occlusive lesions requiring use of re-entry device, lesion length ≤ 120 mm Long Lesion Substudy: For occlusive lesions requiring use of re-entry device, lesion length > 120 mm and ≤ 170 mm Target lesion located at least three centimeters above the inferior edge of the femur Patent infrapopliteal and popliteal artery, i.e., single vessel runoff or better with at least one of three vessels patent (<50% stenosis) to the ankle or foot with no planned intervention. Exclusion Criteria: Previously stented target lesion/vessel. Target lesion/vessel previously treated with drug-coated balloon <12 months prior to randomization/enrollment. Subjects who have undergone prior surgery of the SFA/PPA in the target limb to treat atherosclerotic disease. Use of atherectomy, laser or other debulking devices in the target limb SFA/PPA during the index procedure. History of major amputation in the target limb. Documented life expectancy less than 24 months due to other medical co-morbid condition(s) that could limit the subject's ability to participate in the clinical trial, limit the subject's compliance with the follow-up requirements, or impact the scientific integrity of the clinical trial. Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated. Known hypersensitivity/allergy to the investigational stent system or protocol related therapies (e.g., nitinol, paclitaxel, or structurally related compounds, polymer or individual components, and antiplatelet, anticoagulant, thrombolytic medications). Platelet count <80,000 mm3 or >600,000 mm3 or history of bleeding diathesis. Concomitant renal failure with a serum creatinine >2.0 mg/dL. Receiving dialysis or immunosuppressant therapy. History of myocardial infarction (MI) or stroke/cerebrovascular accident (CVA) within 6 months prior to randomization/enrollment. Unstable angina pectoris at the time of randomization/enrollment. Pregnant, breast feeding, or plan to become pregnant in the next 5 years. Current participation in another investigational drug or device clinical study that has not completed the primary endpoint at the time of randomization/enrollment or that clinically interferes with the current study endpoints (Note: studies requiring extended follow-up for products that were investigational, but have become commercially available since then are not considered investigational studies). Septicemia at the time of randomization/enrollment. Presence of other hemodynamically significant outflow lesions in the target limb requiring intervention within 30 days of randomization/enrollment. Presence of aneurysm in the target vessel. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to randomization/enrollment. Perforated vessel as evidenced by extravasation of contrast media prior to randomization/enrollment. Heavily calcified lesions.

Ages Eligible for Study
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Minimum Age: 18 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: ELUVIA Stent Implantation<br>Percutaneous stent placement in the SFA/PPA | Device: ELUVIA (Stent Implantation)<br>* Drug-eluting self-expanding stent implantation during the index procedure.<br>|
| Active Comparator: Zilver PTX Stent Implantation<br>Percutaneous stent placement in the SFA/PPA | Device: Zilver PTX (Stent Implantation)<br>* Drug-eluting self-expanding stent implantation during the index procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Major Adverse Events (MAEs) | MAEs defined as all causes of death through 1 month, target limb major amputation through 12 months and/or target lesion revascularization (TLR) through 12 months | 12 Months | 
| Number of Participants Reaching Primary Patency | Primary patency of target lesion at 12-months assessed by duplex ultrasound and adjudicated by an independent core laboratory | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CEC-adjudicated Events Through 12 Months | Denominators for the cumulative rate will be based on 1) subjects with events, and 2) subjects with no events but their follow-up time reach on (or beyond) the earliest visit window. | 12 Months | 
| Count of Participants Meeting Primary Sustained Clinical Improvement | Defined as improvement in Rutherford classification (defined as chronic, symptomatic lower limb ischemia in categories 2, 3 or 4) by one or more categories compared with baseline, without target lesion revascularization. | 12 Months | 
| Number of Participants With Hemodynamic Improvement | Defined as an increase in the ankle-brachial index by greater than of equal to 0.10 compared with baseline or to an ankle-brachial index of greater than or equal to 0.90, without need for repeat target lesion revascularization. | 12 Months | 
| Walking Impairment Questionnaire (WIQ) Scores | The WIQ is a functional-assessment questionnaire that evaluates walking ability with regard to speed, distance and stair climbing ability as well as the reasons that walking ability might be limited. Range of scores is between 0% and 100% with 100% being the best and 0% being the worst score. WIQ scores reported as change from baseline. | Baseline to 12 Months | 
| 6-Minute Walk Test - Distance Walked | Change in distance walked from baseline to 12 months. | Change in baseline to 12-Months | 
| 6-Minute Walk Test - Speed | Change in speed walked from baseline to 12 months | Baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atherosclerosis, Superficial Femoral Artery (SFA), Proximal Popliteal Artery (PPA), lower extremities, stenting, paclitaxel