RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty

Boston Scientific Corporation440 enrolled

Overview

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.

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 Drug-Coated Balloon (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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

440

Conditions

Peripheral Artery Disease Atherosclerosis Artery Diseases, Peripheral

Interventions

RANGER™ Paclitaxel Coated BalloonDEVICE

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.

PaclitaxelDRUG

The RANGER™ Balloon is coated with the drug Paclitaxel.

Standard Balloon AngioplastyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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; 2. Subject at least 20 years of age; 3. Chronic symptomatic lower limb ischemia defined as Rutherford classification 2, 3, or 4; 4. Target lesion is in the native SFA and/or PPA down to the P1 segment; 5. 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; 6. Reference vessel diameter ≥ 4 mm and ≤ 8 mm by visual estimate; 7. 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: 1. Life expectancy, documented in the Investigator's opinion, of less than 12 months; 2. Hemorrhagic stroke or cardiac event (e.g. STEMI, unstable angina) within 6 months prior to enrollment; 3. Known allergies or sensitivities to heparin, aspirin, other anticoagulant/antiplatelet therapies, and/or paclitaxel; 4. Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated; 5. Chronic renal insufficiency with serum creatinine \> 2.0 mg/dL within 30 days of index procedure or treatment with dialysis; 6. Platelet count \< 80,000 mm 3 or \> 600,000 mm 3 or history of bleeding diathesis; 7. Receiving immunosuppressive therapy; 8. Septicemia at the time of enrollment; 9. Any major intervention planned within 30 days post index procedure; 10. Presence of other hemodynamically significant outflow lesions in the target limb requiring intervention within 30 days of enrollment; 11. Failure to successfully cross the target lesion with a guidewire; 12. Failure to successfully pre-dilate the target vessel; 13. 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; 14. History of major amputation in the target limb; 15. 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; 16. Pregnant or breast feeding; 17. Presence of aneurysm in the target vessel; 18. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to enrollment; 19. Patient has significant inflow disease which cannot be treated prior to the target lesion treatment; 20. Patient has perforated targeted vessel as evidenced by extravasation of contrast media; 21. Patient has severe calcification that renders the lesion undilatable; 22. 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.

Locations (67)

Thomas Hospital

Fairhope, Alabama, United States

Rocky Mountain Regional VA Medical Center

Aurora, Colorado, United States

The Vascular Experts

Stratford, Connecticut, United States

Christiana Hospital

Newark, Delaware, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Outcomes

Primary Outcomes

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: There was no prespecified analysis of primary lesion patency.

Time frame: 12 months (RCT); 6 months (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: There was no prespecified analysis of primary safety endpoint.

Time frame: Primary safety endpoint assessed at 12 months for RCT study and at both 6 and 12 months for LB substudy.

Secondary Outcomes

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. RCT Standard Balloon Angioplasty: Device deficiency data is only collected for Ranger DCB; data not collected for Standard PTA group; there is no pre-specified analysis of this outcome for the Standard PTA group.

Time frame: 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.

Time frame: 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.

Time frame: Day 0

Number of Major Adverse Event (MAE) Assessment

MAEs defined as all-cause of death post-index procedure (30-days), target limb major amputation, and/or target lesion revascularization (TLR) through 60-months in RCT. MAEs defined as all-cause of death post-index procedure (30-days), target limb major amputation, and/or target lesion revascularization (TLR) through 12-months in LB substudy. PK Substudy: There was no prespecified analysis of MAEs for PK substudy.

Time frame: 60-months (RCT); 12-months (LB substudy).

Number of Clinical Events Committee (CEC) Adjudicated Events

CEC adjudicated events including death of any cause, target lesion revascularization (TLR), target vessel revascularization (TVR) and target limb amputation (TLA). 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. LB substudy follow-up through 12 month.

Time frame: 1, 6, 12, 24, 36, 48 and 60 months (RCT and PK substudy); 1, 6 and 12 months (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. LB Substudy: Follow-up through 12-month. PK Substudy: There was no prespecified analysis of Rate of Primary Sustained Clinical Improvement for PK substudy.

Time frame: 1, 6, 12, 24 and 36 months post-procedure (RCT); 1, 6 and 12 months post-procedure (LB substudy).

Number of Participants With Rate of Secondary 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 including those subjects with repeat TLR. LB Substudy: Follow-up through 12-months. PK Substudy: There was no prespecified analysis of Rate of Secondary Sustained Clinical Improvement for PK substudy.

Time frame: 1, 6, 12, 24 and 36 months post-procedure (RCT): 1, 6, and 12 months post-procedure (LB substudy)

Number of Participants With Rate of Hemodynamic Improvement as Assessed by Changes in Ankle Brachial Index (ABI) From Baseline.

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. LB Substudy: Follow-up through 12-months. PK Substudy: There was no prespecified analysis of Rate of Hemodynamic Improvement for PK substudy.

Time frame: 1, 6, 12, 24, and 36 months post-procedure (RCT); 1, 6, and 12 months post-procedure (LB substudy)

Walking Improvement (Distance) at 6 and 12 Months as Assessed by Change in Six Minute Walk Test (6MWT) From Baseline

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. LB Substudy: There was no prespecified analysis of Walking Improvement (distance) for the LB substudy. PK Substudy: There was no prespecified analysis of Walking Improvement (distance) for PK substudy.

Time frame: 6 and 12 months post-procedure (RCT)

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. LB Substudy: There was no prespecified analysis of Walking Improvement for the LB substudy. PK Substudy: There was no prespecified analysis of Walking Improvement for the PK substudy.

Time frame: 1, 6, 12, 24 and 36 months post-procedure (RCT)

Duplex-defined Binary Restenosis (PSVR > 2.4) of the Target Lesion

Duplex-defined binary restenosis (PSVR \> 2.4) of the target lesion at 1, 6, 12, 24 and 36 Months (RCT) Duplex-defined binary restenosis (PSVR \> 2.4) of the target lesion at 1, 6, and 12 (LB Substudy) PK Substudy: There was no prespecified analysis of duplex defined binary restenosis of the target lesion

Time frame: 1, 6, 12, 24, and 36-months post-procedure (RCT); 1, 6, and 12-months post-procedure (LB substudy)

Patient Utility Values as Assessed by Change in EQ-5D From Baseline.

Patient Utility Values as assessed by change in EQ-5D from baseline at 1, 6, 12, 24 and 36-months post-procedure. The EuroQOL (EQ)-5D is a multi-attribute health classification system. The EQ-5D uses a 5-dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) descriptive system, which each consisting of 5 response options (no problems, slight problems, moderate problems, severe problems, or extreme problems/inability to perform). Outcomes reported as "Improvement" defined as improving at least one category from baseline. LB Substudy: There was no prespecified analysis of Patient Utility Values for the LB Substudy. PK Substudy: There was no prespecified analysis of Patient Utility Values for the PK Substudy.

Time frame: 1, 6, 12, 24 and 36-months post-procedure (RCT).

Changes in Healthcare Utilization Over Time

Changes in healthcare utilization over time as measured by hospitalization readmission. Readmission Rate represents (# of subjects/Total enrolled subjects) who were hospitalized due to TLR/TVR or due to Procedure/Device related AE. LB Substudy: Follow-up through 12 Month. PK Substudy: There was no prespecified analysis of healthcare utilization over time for the PK Substudy.

Time frame: 1, 6, 12, 24, 36, 48 and 60-months post-procedure (RCT); 1, 6, 12-months post-procedure (LB substudy)

PK Parameters Paclitaxel (PTx) Dose

Summary of Pharmacokinetic Parameters in PK substudy. Paclitaxel (PTx) Dose PK parameter data not collected or analyzed in RCT or LB substudy.

Time frame: Time points for analysis are a venous blood draw at screening, followed by blood draws at 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours and 24 or 48 hours after last Ranger DCB balloon removal, as well as 7 days and 30 days post index procedure.

PK Parameters - Maximum Plasma Concentration

Summary of Pharmacokinetic Parameters in PK substudy. cmax (ng/mL) = Maximum plasma concentration PK data not collected or analyzed in RCT or LB substudy.

PK Parameters - Tmax

Summary of Pharmacokinetic Parameters in PK substudy. - Tmax Tmax (h) = The timepoint where cmax is reached PK parameter data not collected or analyzed in RCT or LB substudy.

PK Parameters - Area Under the Blood Concentration Versus Time Curve From Time Zero up to the Time of the Last Quantifiable Concentration, Calculated by Trapezoidal Methods.

Summary of Pharmacokinetic Parameters in PK substudy. AUC0-t (ng\*h/mL) = Area under the blood concentration versus time curve from time zero up to the time of the last quantifiable concentration, calculated by trapezoidal methods. PK parameter data not collected or analyzed in RCT or LB substudy.