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

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.

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.