RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty

Atherosclerosis Clinical Trial

— RANGER II SFA  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03064126
• Other study ID #: S2062
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2017
• Est. completion date: October 25, 2023

Study information

• Verified date: April 2024
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: October 25, 2023
• Est. primary completion date: November 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Device:
• RANGER™ Paclitaxel Coated Balloon
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.

Drug:
• Paclitaxel
The RANGER™ Balloon is coated with the drug Paclitaxel.

Procedure:
• Standard Balloon Angioplasty
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.

Locations

Country	Name	City	State
Austria	Medizinische Univ.-Kliniken Graz	Graz
Austria	Allgemeines Krankenhaus AKH	Vienna
Austria	Hanusch-Krankenhaus	Vienna
Belgium	Ziekenhuis Oost Limburg	Genk
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Regionaal Ziekenhuis Heilig Hart Tienen	Tienen
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Hopital Saint - Francois d'Assise	Quebec
Canada	Fleurimont Hospital	Sherbrooke	Quebec
Japan	Kansai Rosai Hospital	Amagasaki	Hyogo-ken
Japan	Iwaki City Medical Center	Iwaki	Fukushima
Japan	Kasukabe Chuo General Hospital	Kasukabe	Saitama
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Kokura Memorial Hospital	Kitakyushu	Fukuoka
Japan	Kyoto Katsura Hospital	Kyoto
Japan	Saiseikai Central Hospital	Minato	Tokyo
Japan	Morinomiya Hospital	Osaka
Japan	Osaka Saiseikai Nakatsu Hospital	Osaka
Japan	Tokeidai Memorial Hospital	Sapporo	Hokkaido
Japan	Sendai Kousei Hospital	Sendai	Miyagi
Japan	Saiseikai Yokohama-City Eastern Hospital	Yokohama	Kanagawa
New Zealand	Auckland City Hospital	Auckland
New Zealand	Clinical Trials NZ	Hamilton
New Zealand	Middlemore Hospital	Otahuhu
United States	King's Daughters Medical Center - Kentucky Heart Institute	Ashland	Kentucky
United States	Rocky Mountain Regional VA Medical Center	Aurora	Colorado
United States	St. Charles Medical Center	Bend	Oregon
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	South Florida Vascular Associates	Coconut Creek	Florida
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	North Park Heart & Vascular Center	Dallas	Texas
United States	Premier Cardiovascular Institute	Dayton	Ohio
United States	Thomas Hospital	Fairhope	Alabama
United States	St. Joseph Hospital	Fort Wayne	Indiana
United States	North Florida Regional Medical Center	Gainesville	Florida
United States	University Medical Center-Greenville Memorial Hospital	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Kaiser Foundation Hospitals	Honolulu	Hawaii
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Turkey Creek Medical Center	Knoxville	Tennessee
United States	Davis Hospital and Medical Center	Layton	Utah
United States	Cardiology Clinic of San Antonio	Live Oak	Texas
United States	Texas Tech University Health Sciences Center	Lubbock	Texas
United States	Wellstar Hospitals	Marietta	Georgia
United States	North Dallas Research Associates	McKinney	Texas
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Community Hospital	Munster	Indiana
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Mount Sinai Medical Center	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	AdventHealth Orlando	Orlando	Florida
United States	Temple University	Philadelphia	Pennsylvania
United States	The Heart Hospital Baylor Plano	Plano	Texas
United States	THR Presbyterian Plano	Plano	Texas
United States	Rex Hospital	Raleigh	North Carolina
United States	United Heart and Vascular Clinic	Saint Paul	Minnesota
United States	AdventHealth Sebring	Sebring	Florida
United States	Staten Island University Hospital	Staten Island	New York
United States	The Vascular Experts	Stratford	Connecticut
United States	Tyler Cardiac and Endovascular Center	Tyler	Texas
United States	Washington Hospital Center	Washington	District of Columbia
United States	Aspirus Heart and Vascular Institute	Wausau	Wisconsin
United States	Northeast Ohio Vascular Associates, Inc.	Willoughby	Ohio
United States	Coastal Carolina Surgical Associates	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Japan,  New Zealand, 

References & Publications (5)

Kakkar AM, Abbott JD. Percutaneous versus surgical management of lower extremity peripheral artery disease. Curr Atheroscler Rep. 2015;17(2):479. doi: 10.1007/s11883-014-0479-0. — View Citation

Laird JR, Katzen BT, Scheinert D, Lammer J, Carpenter J, Buchbinder M, Dave R, Ansel G, Lansky A, Cristea E, Collins TJ, Goldstein J, Jaff MR; RESILIENT Investigators. Nitinol stent implantation versus balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal artery: twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv. 2010 Jun 1;3(3):267-76. doi: 10.1161/CIRCINTERVENTIONS.109.903468. Epub 2010 May 18. — View Citation

Litsky J, Chanda A, Stilp E, Lansky A, Mena C. Critical evaluation of stents in the peripheral arterial disease of the superficial femoral artery - focus on the paclitaxel eluting stent. Med Devices (Auckl). 2014 May 28;7:149-56. doi: 10.2147/MDER.S45472. eCollection 2014. — View Citation

Razavi MK, Mustapha JA, Miller LE. Contemporary systematic review and meta-analysis of early outcomes with percutaneous treatment for infrapopliteal atherosclerotic disease. J Vasc Interv Radiol. 2014 Oct;25(10):1489-96, 1496.e1-3. doi: 10.1016/j.jvir.2014.06.018. Epub 2014 Aug 15. — View Citation

Scheinert D, Duda S, Zeller T, Krankenberg H, Ricke J, Bosiers M, Tepe G, Naisbitt S, Rosenfield K. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon angioplasty. JACC Cardiovasc Interv. 2014 Jan;7(1):10-9. doi: 10.1016/j.jcin.2013.05.022. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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