Clinical trial NCT03064126: RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peripheral Artery Disease
Atherosclerosis
Artery Diseases, Peripheral
Plaque, Atherosclerotic
Occlusive Arterial Disease
Keywords: Artery
Atherosclerosis
Arterial
Peripheral
Plaque
Angioplasty
PTA
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2017-02-24
Enrollment: 440
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The RANGER™ investigational device is coated with the drug paclitaxel.
Primary purpose: TREATMENT

Brief 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.

Detailed 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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Primary Lesion Patency
timeFrame: 12 months (RCT); 6 months (LB substudy)
measure: Major Adverse Events (MAEs) (Primary Safety Endpoint)
timeFrame: Primary safety endpoint assessed at 12 months for RCT study and at both 6 and 12 months for LB substudy.
Secondary outcomes:
measure: Number of Participants With Technical Success of Angioplasty Procedure
timeFrame: Day 0
measure: Number of Participants With Procedural Success of Angioplasty Procedure
timeFrame: Day 0
measure: Number of Participants With Clinical Success Rate Assessment
timeFrame: Day 0
measure: Number of Major Adverse Event (MAE) Assessment
timeFrame: 60-months (RCT); 12-months (LB substudy).
measure: Number of Clinical Events Committee (CEC) Adjudicated Events
timeFrame: 1, 6, 12, 24, 36, 48 and 60 months (RCT and PK substudy); 1, 6 and 12 months (LB substudy)
measure: Number of Participants With Rate of Primary Sustained Clinical Improvement as Assessed by Changes in Rutherford Classification From Baseline
timeFrame: 1, 6, 12, 24 and 36 months post-procedure (RCT); 1, 6 and 12 months post-procedure (LB substudy).
measure: Number of Participants With Rate of Secondary Sustained Clinical Improvement as Assessed by Changes in Rutherford Classification From Baseline.
timeFrame: 1, 6, 12, 24 and 36 months post-procedure (RCT): 1, 6, and 12 months post-procedure (LB substudy)
measure: Number of Participants With Rate of Hemodynamic Improvement as Assessed by Changes in Ankle Brachial Index (ABI) From Baseline.
timeFrame: 1, 6, 12, 24, and 36 months post-procedure (RCT); 1, 6, and 12 months post-procedure (LB substudy)
measure: Walking Improvement (Distance) at 6 and 12 Months as Assessed by Change in Six Minute Walk Test (6MWT) From Baseline
timeFrame: 6 and 12 months post-procedure (RCT)
measure: Walking Improvement Assessed by Change in Walking Impairment Questionnaire (WIQ) From Baseline.
timeFrame: 1, 6, 12, 24 and 36 months post-procedure (RCT)
measure: Duplex-defined Binary Restenosis (PSVR > 2.4) of the Target Lesion
timeFrame: 1, 6, 12, 24, and 36-months post-procedure (RCT); 1, 6, and 12-months post-procedure (LB substudy)
measure: Patient Utility Values as Assessed by Change in EQ-5D From Baseline.
timeFrame: 1, 6, 12, 24 and 36-months post-procedure (RCT).
measure: Changes in Healthcare Utilization Over Time
timeFrame: 1, 6, 12, 24, 36, 48 and 60-months post-procedure (RCT); 1, 6, 12-months post-procedure (LB substudy)
measure: PK Parameters Paclitaxel (PTx) Dose
timeFrame: 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.
measure: PK Parameters - Maximum Plasma Concentration
timeFrame: 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.
measure: PK Parameters - Tmax
timeFrame: 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.
measure: 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.
timeFrame: 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.
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: Thomas Hospital
state: Alabama
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center
state: Colorado
city: Stratford
country: United States
facility: The Vascular Experts
state: Connecticut
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Coconut Creek
country: United States
facility: South Florida Vascular Associates
state: Florida
city: Gainesville
country: United States
facility: North Florida Regional Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Sebring
country: United States
facility: AdventHealth Sebring
state: Florida
city: Marietta
country: United States
facility: Wellstar Hospitals
state: Georgia
city: Honolulu
country: United States
facility: Kaiser Foundation Hospitals
state: Hawaii
city: Fort Wayne
country: United States
facility: St. Joseph Hospital
state: Indiana
city: Munster
country: United States
facility: Community Hospital
state: Indiana
city: Ashland
country: United States
facility: King's Daughters Medical Center - Kentucky Heart Institute
state: Kentucky
city: Houma
country: United States
facility: Terrebonne General Medical Center
state: Louisiana
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Heart and Vascular Clinic
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Raleigh
country: United States
facility: Rex Hospital
state: North Carolina
city: Wilmington
country: United States
facility: Coastal Carolina Surgical Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Dayton
country: United States
facility: Premier Cardiovascular Institute
state: Ohio
city: Willoughby
country: United States
facility: Northeast Ohio Vascular Associates, Inc.
state: Ohio
city: Bend
country: United States
facility: St. Charles Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Greenville
country: United States
facility: University Medical Center-Greenville Memorial Hospital
state: South Carolina
city: Knoxville
country: United States
facility: Turkey Creek Medical Center
state: Tennessee
city: Dallas
country: United States
facility: North Park Heart & Vascular Center
state: Texas
city: Live Oak
country: United States
facility: Cardiology Clinic of San Antonio
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: McKinney
country: United States
facility: North Dallas Research Associates
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Plano
country: United States
facility: THR Presbyterian Plano
state: Texas
city: Tyler
country: United States
facility: Tyler Cardiac and Endovascular Center
state: Texas
city: Layton
country: United States
facility: Davis Hospital and Medical Center
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Hospitals
state: West Virginia
city: Wausau
country: United States
facility: Aspirus Heart and Vascular Institute
state: Wisconsin
city: Graz
country: Austria
facility: Medizinische Univ.-Kliniken Graz
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus AKH
city: Vienna
country: Austria
facility: Hanusch-Krankenhaus
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Tienen
country: Belgium
facility: Regionaal Ziekenhuis Heilig Hart Tienen
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: Fleurimont Hospital
state: Quebec
city: Quebec
country: Canada
facility: Hopital Saint - Francois d'Assise
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Iwaki
country: Japan
facility: Iwaki City Medical Center
state: Fukushima
city: Sapporo
country: Japan
facility: Tokeidai Memorial Hospital
state: Hokkaido
city: Amagasaki
country: Japan
facility: Kansai Rosai Hospital
state: Hyogo-ken
city: Yokohama
country: Japan
facility: Saiseikai Yokohama-City Eastern Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Kasukabe
country: Japan
facility: Kasukabe Chuo General Hospital
state: Saitama
city: Minato
country: Japan
facility: Saiseikai Central Hospital
state: Tokyo
city: Kyoto
country: Japan
facility: Kyoto Katsura Hospital
city: Osaka
country: Japan
facility: Morinomiya Hospital
city: Osaka
country: Japan
facility: Osaka Saiseikai Nakatsu Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Clinical Trials NZ
city: Otahuhu
country: New Zealand
facility: Middlemore Hospital
Study officials:
affiliation: Universitaets-Herzzentrum
name: Thomas Zeller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina - Rex Hospital
name: Ravish Sachar, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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.
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.
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.
citation: Schroe H, Sachar R, Keirse K, Soga Y, Brodmann M, Rao V, Werner M, Holden A, Lopez L, Krishnan P, Diaz-Cartelle J. The RANGER II superficial femoral artery trial: 1-year results of the long lesion cohort. Vasc Med. 2022 Oct;27(5):457-465. doi: 10.1177/1358863X221097164. Epub 2022 Aug 9.
citation: Soga Y, Fujihara M, Yamamoto Y, Nakamura S, Iida O, Kawasaki D, Urasawa K, Ando H, Mori S, Suzuki K, Horie K, Diaz-Cartelle J, Kozuki A. One-year results for Japanese patients in RANGER II SFA. Heart Vessels. 2022 Apr;37(4):568-573. doi: 10.1007/s00380-021-01947-3. Epub 2021 Sep 23.
citation: Sachar R, Soga Y, Ansari MM, Kozuki A, Lopez L, Brodmann M, Schroe H, Ramanath VS, Diaz-Cartelle J, Zeller T; RANGER II SFA Investigators. 1-Year Results From the RANGER II SFA Randomized Trial of the Ranger Drug-Coated Balloon. JACC Cardiovasc Interv. 2021 May 24;14(10):1123-1133. doi: 10.1016/j.jcin.2021.03.021.