RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty

Study Overview
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Brief Summary
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To evaluate the safety and effectiveness of the Ranger™ Paclitaxel Coated Balloon for treating lesions located in the superficial femoral and proximal popliteal arteries (SFA/PPA). Long Balloon substudy: To evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) Ranger™ Paclitaxel Coated Balloon in the 120, 150 and 200 mm lengths for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions.

Detailed Description
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The RANGER II SFA is a global, prospective, multi-center clinical trial. Approximately 446 subjects will be enrolled at up to 80 study centers worldwide. Regions participating include the United States, Canada, European Union, Japan and New Zealand. The trial consists of a single-blind, superiority, 3:1 (Ranger DCB vs. Standard PTA) randomized controlled trial (RCT) and a concurrent, non-randomized, single-arm, pharmacokinetic (PK) substudy, and a concurrent, non-blinded, non-randomized, Long balloon substudy.

Official Title
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RANGER II SFA: A 3:1 Randomized Trial Comparing the Boston Scientific RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty for the Treatment of Superficial Femoral Arteries (SFA) and Proximal Popliteal Arteries (PPA)

Conditions
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Peripheral Artery Disease, Atherosclerosis, Artery Diseases, Peripheral, Plaque, Atherosclerotic, Occlusive Arterial Disease

Intervention / Treatment
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* Device: RANGER™ Paclitaxel Coated Balloon
* Drug: Paclitaxel
* Procedure: Standard Balloon Angioplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject (or Legal Guardian) is willing and able to provide consent before any study-specific tests or procedures are performed and agree to attend all required follow-up visits; Subject at least 20 years of age; Chronic symptomatic lower limb ischemia defined as Rutherford classification 2, 3, or 4; Target lesion is in the native SFA and/or PPA down to the P1 segment; Patent popliteal and infrapopliteal arteries, i.e., single vessel runoff or better with at least one of three vessels patent (less than 50 % stenosis) to the ankle or foot; Reference vessel diameter ≥ 4 mm and ≤ 8 mm by visual estimate; Angiographic evidence that target lesion consists of a single de novo, non-stented and non-atherectomy treated or restenotic lesion (or tandem lesions or a combination lesion as defined below) that is: ≥ 70%-99% stenotic with total lesion length up to 180 mm by visual estimate. Occluded with total lesion length ≤ 100 mm by visual estimate. If lesion is restenotic, most recent PTA treatment must be > 3 months prior to enrollment. Exclusion Criteria: Life expectancy, documented in the Investigator's opinion, of less than 12 months; Hemorrhagic stroke or cardiac event (e.g. STEMI, unstable angina) within 6 months prior to enrollment; Known allergies or sensitivities to heparin, aspirin, other anticoagulant/antiplatelet therapies, and/or paclitaxel; Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated; Chronic renal insufficiency with serum creatinine > 2.0 mg/dL within 30 days of index procedure or treatment with dialysis; Platelet count < 80,000 mm 3 or > 600,000 mm 3 or history of bleeding diathesis; Receiving immunosuppressive therapy; Septicemia at the time of enrollment; Any major intervention planned within 30 days post index procedure; Presence of other hemodynamically significant outflow lesions in the target limb requiring intervention within 30 days of enrollment; Failure to successfully cross the target lesion with a guidewire; Failure to successfully pre-dilate the target vessel; Patient has lesion that requires the use of adjunctive primary treatment modalities (i.e. laser, atherectomy, scoring/cutting balloon, other debulking devices, etc.) during the index procedure; History of major amputation in the target limb; Target lesion or vessel has ever been previously treated with stent (e.g. in-stent restenosis) or surgery. Target lesion or vessel has been treated with atherectomy or a DCB in the past 12 months; Pregnant or breast feeding; Presence of aneurysm in the target vessel; Acute ischemia and/or acute thrombosis of the SFA/PPA prior to enrollment; Patient has significant inflow disease which cannot be treated prior to the target lesion treatment; Patient has perforated targeted vessel as evidenced by extravasation of contrast media; Patient has severe calcification that renders the lesion undilatable; Current participation in another investigational drug or device clinical trial that has not completed the primary endpoint at the time of randomization/enrollment or that clinically interferes with the current trial endpoints.

Ages Eligible for Study
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Minimum Age: 20 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
Interventional Model Description: The RANGER™ investigational device is coated with the drug paclitaxel.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RANGER™ Paclitaxel Coated Balloon<br>RANGER™ Paclitaxel Coated Balloon Catheter angioplasty in the SFA/PPA at the index procedure. Subjects will be randomized 3:1 to the drug coated or standard angioplasty balloon. | Device: RANGER™ Paclitaxel Coated Balloon<br>* A procedure that utilizes a balloon coated with paclitaxel (drug) which can open up a blocked blood vessel using a small, flexible plastic tube, or catheter, with a balloon at the end of it. When the tube is in place, it inflates to open the blood vessel, or artery, so that normal blood flow is restored. The tube is then removed. The blood vessels that will be treated in the RANGER II SFA study include the superficial femoral arteries and the proximal popliteal arteries.<br>* Other names: Percutaneous Transluminal Angioplasty (PTA);Drug: Paclitaxel<br>* The RANGER™ Balloon is coated with the drug Paclitaxel.<br>|
| Active Comparator: Standard Balloon Angioplasty<br>Standard Balloon Catheter angioplasty in the SFA/PPA at the index procedure. Subjects will be randomized 3:1 to the drug coated or standard angioplasty balloon. | Procedure: Standard Balloon Angioplasty<br>* A procedure that utilizes an uncoated balloon which can open up a blocked blood vessel using a small, flexible plastic tube, or catheter, with a balloon at the end of it. When the tube is in place, it inflates to open the blood vessel, or artery, so that normal blood flow is restored. The tube is then removed. The blood vessels that will be treated in the RANGER II SFA study include the superficial femoral arteries and the proximal popliteal arteries.<br>* Other names: Percutaneous Transluminal Angioplasty (PTA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Primary Lesion Patency | RCT outcome measure: Primary patency of the target lesion is determined by Peak Systolic Velocity Ratio (PSVR) ≤ 2.4 (by duplex ultrasound (DUS)) and freedom from clinically-driven Target Lesion Revascularization (TLR) within 12 months from procedure. Lesion patency is defined as freedom from more than 50% stenosis based on DUS PSVR comparing data within the treated segment to the proximal normal arterial segment. PSVR >2.4 suggests >50% stenosis. LB Substudy outcome measure: Primary patency of the target lesion is determined by duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤ 2.4 in absence of clinically-driven TLR. Primary effectiveness endpoint is assessed at 6 months post-procedure. PK Substudy not analyzed for primary patency. | 12 months (6 months for LB substudy) | 
| Major Adverse Events (MAEs) (Primary Safety Endpoint) | RCT: MAE is defined as a composite of freedom from all-cause death through 1 month, target limb major amputation (defined as at or above the ankle) within 12 months, and/or Target Lesion Revascularization (TLR) within 12 months. LB Substudy: Primary safety endpoint assesses the occurrence of MAE defined as all-cause death through 1 month, target limb major amputation and/or TLR at 6 and 12 months post-index procedure. PK Substudy: Not analyzed for primary safety endpoint. | 12 months (6 months for LB substudy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Technical Success of Angioplasty Procedure | Technical success defined as successful delivery, balloon inflation and deflation and retrieval of the intact trial device without burst below the rated burst pressure. | Day 0 | 
| Number of Participants With Procedural Success of Angioplasty Procedure | Procedural success defined as residual stenosis of less than or equal to 50% (non-stented subjects) or less than or equal to 30% (stented subjects) by core laboratory evaluation. | Day 0 | 
| Number of Participants With Clinical Success Rate Assessment | Clinical success defined as procedural success without procedural complications including death, major target limb amputation, thrombosis of the target lesion, or clinically-driven TLR prior to discharge. | Day 0 | 
| Number of Major Adverse Event (MAE) Assessment | MAEs defined as all-cause of death post-index procedure, target limb major amputation, and/or target lesion revascularization (TLR). | 12 months (6 months for LB substudy) | 
| 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 reaches (or is beyond) the earliest visit window. | 12 months (6 Months for LB Substudy) | 
| Number of Participants With Rate of Primary Sustained Clinical Improvement as Assessed by Changes in Rutherford Classification From Baseline | Endpoint determined to be a success when there is an improvement in Rutherford Classification of one or more categories as compared to pre-procedure without the need for repeat TLR | 12 months (6 months for LB substudy) | 
| Number of Participants With Rate of Secondary Sustained Clinical Improvement as Assessed by Changes in Rutherford Classification | Endpoint determined to be a success when there is an improvement in Rutherford Classification of one or more categories as compared to pre-procedure including those subjects with repeat TLR | 12 months (6 months for LB substudy) | 
| Number of Participants With Rate of Hemodynamic Improvement as Assessed by Changes in Ankle Brachial Index (ABI) | Improvement of ABI by ≥ 0.1 or to an ABI ≥ 0.90 as compared to the pre-procedure value without the need for repeat revascularization. | 12 months (6 months for LB substudy) | 
| Walking Improvement (Distance) Assessed by Change in Six Minute Walk Test (6MWT) | The 6MWT measure the maximal walking distance that a patient achieves on a flat, hard surface within a period of 6 minutes. It evaluates the global and integrated responses of all physiological systems involved during exercise including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, neuromuscular units and muscle metabolism. Change in distance walked from baseline to 12 months. | 12 months | 
| Walking Improvement Assessed by Change in Walking Impairment Questionnaire (WIQ) From Baseline | The WIQ is a functional assessment questionnaire that evaluates walking ability with regard to speed, distance and stair climbing ability. It also assesses the reasons that walking ability might be limited. Range of scores include 0% (worst score) to 100% (best score). Walking improvement change assessed from baseline to 12 months. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artery, Atherosclerosis, Arterial, Peripheral, Plaque, Angioplasty, PTA