The DES BTK Vascular Stent System vs PTA in Subjects With Critical Limb Ischemia

NCT03551496 | Completed Phase 3 Results DMC FDA Device

• 1 other identifier: S2348
• Study Type: interventional
• Target: 201
• Locations: 5 countries
• Sites: 42

Brief Summary

Single phased global, prospective, multicenter clinical trial designed to demonstrate a superior patency rate and acceptable safety in below the knee arteries with lesions treated with the DES BTK Vascular Stent System vs. percutaneous transluminal angioplasty (PTA).

Conditions

Critical Limb Ischemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Primary Patency

  Twelve-Month Primary Patency defined as a binary endpoint to be determined via duplex ultrasound (DUS) measuring flow at the 12-month follow-up visit, in the absence of clinically-driven target lesion revascularization (TLR) or bypass of the target lesion. Data table consists of the number of participants with flow as assessed by DUS.

  12 months

• Number of Participants Free From Major Adverse Events (MAE)

  The primary safety endpoint assesses freedom from major adverse events (MAE) at 12 months post-procedure. (MAE is defined as: above ankle amputation in index limb; major re-intervention; and perioperative (30 day) mortality)

  12 months

Other Outcomes (10)

• Number of Participants With Assisted Primary Patency

  12 months post procedure

• Number of Participants With Clinically Driven Target Lesion Revascularization

  12 months post procedure

• Number of Participants With Major Amputation (Defined as Amputation of the Lower Limb at the Ankle Level or Above)

  12 months post procedure

Study Arms (2)

DES BTK

EXPERIMENTAL

Treatment with DES BTK

Combination Product: Drug Eluting Stent - Below the Knee

Conventional PTA

ACTIVE COMPARATOR

Treatment with standard PTA

Device: Standard PTA Control Arm

Interventions

Drug Eluting Stent - Below the Knee COMBINATION_PRODUCT

Treatment arm with DES-BTK, starting with one size of the device - 3.5 mm X 80 mm

DES BTK

Standard PTA Control Arm DEVICE

The PTA device used must be market-released in the investigational center's geography and the size (ie, diameter, balloon length and catheter length) will be determined by the investigator.

Conventional PTA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is 18 years or older and has signed and dated the trial informed consent form (ICF)
• Subject is willing and able to comply with the trial testing, procedures and follow-up schedule
• Subject has chronic, symptomatic lower limb ischemia, determined by Rutherford categories 4 or 5 in the target limb, with wound(s) confined to toes/forefoot
• Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually active must be using, or agree to use, a medically-acceptable method of birth control as confirmed by the investigator
• Stenotic, restenotic or occlusive target lesion(s) located in the tibioperoneal trunk, anterior tibial, posterior tibial and/or peroneal artery(ies).
• Target lesion(s) must be at least 4cm above the ankle joint
• A single target lesion per vessel, in up to 2 vessels, in a single limb
• Degree of stenosis ≥ 70% by visual angiographic assessment
• Reference vessel diameter is between 2.5 - 3.25mm for phase A RCT
• Total target lesion length (or series of lesion segments) to be treated is ≤ 70 mm for phase A RCT prior to the data monitoring committee's approval for stent overlap. (Note: Lesion segment(s) must be fully covered with one DES BTK stent, if randomized to stent)
• Total target lesion length (or series of lesion segments) to be treated is ≤ 140 mm for phase A RCT after the data monitoring committee's approval for stent overlap (Note: Lesion segment(s) must be fully covered with up to two DES BTK stents, if randomized to stent)
• Target vessel(s) reconstitute(s) at or above the stenting limit zone (4cm above the ankle joint)
• Target lesion(s) is located in an area that may be stented without blocking access to patent main branches
• Treatment of all above the knee inflow lesion(s) is successful prior to treatment of the target lesion
• Guidewire has successfully crossed the target lesion(s)

You may not qualify if:

• Life expectancy ≤ 1year
• Stroke ≤ 90 days prior to the procedure date
• Prior or planned major amputation in the target limb
• Previous surgery in the target vessel(s) (including prior ipsilateral crural bypass)
• Previously implanted stent in the target vessel(s)
• Failed PTA of target lesion/vessel ≤ 60 days prior to the procedure date
• Renal failure as measured by a GFR ≤ 30ml/min per 1.73m2, measured ≤ 30 days prior to the procedure date
• Subject has a platelet count ≤ 50 or ≥ 600 X 103/µL ≤ 30 days prior to the procedure date
• NYHA class IV heart failure
• Subject has symptomatic coronary artery disease (ie, unstable angina)
• History of myocardial infarction or thrombolysis ≤ 90 days prior to the procedure date
• Non-atherosclerotic disease resulting in occlusion (eg, embolism, Buerger's disease, vasculitis)
• Subject is currently taking Canagliflozin
• Body Mass Index (BMI) \<18
• Active septicemia or bacteremia

Sponsors & Collaborators

• Boston Scientific Corporation: lead

Study Sites (42)

St. Bernards Medical Center

Jonesboro, Arkansas, 72401, United States

Location

Arkansas Heart Hospital

Little Rock, Arkansas, 72211, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Colorado VA

Denver, Colorado, 80220, United States

Location

Bradenton Cardiology

Bradenton, Florida, 34205, United States

Location

Willis Knighton Bossier Medical Center - Grace Research, LLC

Bossier City, Louisiana, 71111, United States

Location

Cardiovascular Institute of the South Clinical Research Corporation

Houma, Louisiana, 70360, United States

Location

Advanced Cardiac & Vascular Centers for Amputation Prevention

Grand Rapids, Michigan, 49525, United States

Location

United Heart and Vascular Clinic

Saint Paul, Minnesota, 55102, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

New Mexico Heart Institute, PA

Albuquerque, New Mexico, 87102, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Amputation Prevention Center of North Carolina

Cary, North Carolina, 27518, United States

Location

NC Heart and Vascular Research, LLC

Raleigh, North Carolina, 27607, United States

Location

Wake Medical Center

Raleigh, North Carolina, 27610, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

OhioHealth Research and Innovation Institute - Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

Saint Vincent Consultants in Cardiovascular Diseases at St. Vincent Hospital

Erie, Pennsylvania, 16544, United States

Location

Jackson-Madison County General Hospital

Jackson, Tennessee, 38305, United States

Location

Heart Hospital of Austin

Austin, Texas, 78756, United States

Location

Texas Tech University Health

Lubbock, Texas, 79430, United States

Location

THR Presbyterian Plano

Plano, Texas, 75093, United States

Location

AZ Sint-Blasius

Dendermonde, 9200, Belgium

Location

ZOL Genk (Ziekenhuis Oost-Limburg)

Genk, 3600, Belgium

Location

UZ Gent (Universitair Ziekenhuis Gent)

Ghent, 9000, Belgium

Location

CHU Nantes

Nantes, 44000, France

Location

Hopital Paris Saint Joseph

Paris, 75014, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Clinique Pasteur

Toulouse, 31076, France

Location

Tokyo Bay Urayasu Ichikawa Medical Center

Urayasu-shi, Chiba, 279-0001, Japan

Location

Kokura Memorial Hospital

Kitakyushu, Fukuoka, 802-8555, Japan

Location

Asahikawa Medical University Hospital

Asahikawa-shi, Hokkaido, 078-8510, Japan

Location

Kansai Rosai Hospital

Amagasaki, Hyōgo, 660-8511, Japan

Location

Nara Medical University Hospital

Kashihara, Nara, 634-8522, Japan

Location

Kishiwada Tokushukai Hospital

Kishiwada, Osaka, 596-8522, Japan

Location

Tokyo Medical and Dental University, Medical Hospital

Bunkyō-Ku, Tokyo, 113-8510, Japan

Location

Toho University Ohashi Medical Center

Meguro City, Tokyo, 153-8515, Japan

Location

HAGA Ziekenhuis (Haga Ziekenhuis van Den Haag)

The Hague, 2566, Netherlands

Location

Related Publications (19)

• Kolte D, Kennedy KF, Shishehbor MH, Abbott JD, Khera S, Soukas P, Mamdani ST, Hyder ON, Drachman DE, Aronow HD. Thirty-Day Readmissions After Endovascular or Surgical Therapy for Critical Limb Ischemia: Analysis of the 2013 to 2014 Nationwide Readmissions Databases. Circulation. 2017 Jul 11;136(2):167-176. doi: 10.1161/CIRCULATIONAHA.117.027625. Epub 2017 May 2.

  PMID: 28465288 BACKGROUND

• Conte MS, Geraghty PJ, Bradbury AW, Hevelone ND, Lipsitz SR, Moneta GL, Nehler MR, Powell RJ, Sidawy AN. Suggested objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc Surg. 2009 Dec;50(6):1462-73.e1-3. doi: 10.1016/j.jvs.2009.09.044. Epub 2009 Nov 7.

  PMID: 19897335 BACKGROUND

• Scheinert D, Katsanos K, Zeller T, Koppensteiner R, Commeau P, Bosiers M, Krankenberg H, Baumgartner I, Siablis D, Lammer J, Van Ransbeeck M, Qureshi AC, Stoll HP; ACHILLES Investigators. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial. J Am Coll Cardiol. 2012 Dec 4;60(22):2290-5. doi: 10.1016/j.jacc.2012.08.989.

  PMID: 23194941 BACKGROUND

• Spreen MI, Martens JM, Hansen BE, Knippenberg B, Verhey E, van Dijk LC, de Vries JP, Vos JA, de Borst GJ, Vonken EJ, Wever JJ, Statius van Eps RG, Mali WP, van Overhagen H. Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial. Circ Cardiovasc Interv. 2016 Feb;9(2):e002376. doi: 10.1161/CIRCINTERVENTIONS.114.002376.

  PMID: 26861113 BACKGROUND

• Kinlay S. Management of Critical Limb Ischemia. Circ Cardiovasc Interv. 2016 Feb;9(2):e001946. doi: 10.1161/CIRCINTERVENTIONS.115.001946.

  PMID: 26858079 BACKGROUND

• Elsayed S, Clavijo LC. Critical limb ischemia. Cardiol Clin. 2015 Feb;33(1):37-47. doi: 10.1016/j.ccl.2014.09.008.

  PMID: 25439329 BACKGROUND

• Conte MS. Critical appraisal of surgical revascularization for critical limb ischemia. J Vasc Surg. 2013 Feb;57(2 Suppl):8S-13S. doi: 10.1016/j.jvs.2012.05.114.

  PMID: 23336860 BACKGROUND

• Gray BH, Diaz-Sandoval LJ, Dieter RS, Jaff MR, White CJ; Peripheral Vascular Disease Committee for the Society for Cardiovascular Angiography and Interventions. SCAI expert consensus statement for infrapopliteal arterial intervention appropriate use. Catheter Cardiovasc Interv. 2014 Oct 1;84(4):539-45. doi: 10.1002/ccd.25395. Epub 2014 Jul 18.

  PMID: 25045160 BACKGROUND

• Adam DJ, Beard JD, Cleveland T, Bell J, Bradbury AW, Forbes JF, Fowkes FG, Gillepsie I, Ruckley CV, Raab G, Storkey H; BASIL trial participants. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005 Dec 3;366(9501):1925-34. doi: 10.1016/S0140-6736(05)67704-5.

  PMID: 16325694 BACKGROUND

• Popplewell MA, Davies HOB, Narayanswami J, Renton M, Sharp A, Bate G, Patel S, Deeks J, Bradbury AW. A Comparison of Outcomes in Patients with Infrapopliteal Disease Randomised to Vein Bypass or Plain Balloon Angioplasty in the Bypass vs. Angioplasty in Severe Ischaemia of the Leg (BASIL) Trial. Eur J Vasc Endovasc Surg. 2017 Aug;54(2):195-201. doi: 10.1016/j.ejvs.2017.04.020. Epub 2017 Jun 8.

  PMID: 28602580 BACKGROUND

• Sadaghianloo N, Jean-Baptiste E, Declemy S, Mousnier A, Brizzi S, Hassen-Khodja R. Percutaneous angioplasty of long tibial occlusions in critical limb ischemia. Ann Vasc Surg. 2013 Oct;27(7):894-903. doi: 10.1016/j.avsg.2013.02.008.

  PMID: 23993107 BACKGROUND

• Bosiers M, Scheinert D, Peeters P, Torsello G, Zeller T, Deloose K, Schmidt A, Tessarek J, Vinck E, Schwartz LB. Randomized comparison of everolimus-eluting versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial occlusive disease. J Vasc Surg. 2012 Feb;55(2):390-8. doi: 10.1016/j.jvs.2011.07.099. Epub 2011 Dec 14.

  PMID: 22169682 BACKGROUND

• Spreen MI, Martens JM, Knippenberg B, van Dijk LC, de Vries JPM, Vos JA, de Borst GJ, Vonken EPA, Bijlstra OD, Wever JJ, Statius van Eps RG, Mali WPTM, van Overhagen H. Long-Term Follow-up of the PADI Trial: Percutaneous Transluminal Angioplasty Versus Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia. J Am Heart Assoc. 2017 Apr 14;6(4):e004877. doi: 10.1161/JAHA.116.004877.

  PMID: 28411244 BACKGROUND

• de Weger VA, Beijnen JH, Schellens JH. Cellular and clinical pharmacology of the taxanes docetaxel and paclitaxel--a review. Anticancer Drugs. 2014 May;25(5):488-94. doi: 10.1097/CAD.0000000000000093.

  PMID: 24637579 BACKGROUND

• Ng VG, Mena C, Pietras C, Lansky AJ. Local delivery of paclitaxel in the treatment of peripheral arterial disease. Eur J Clin Invest. 2015 Mar;45(3):333-45. doi: 10.1111/eci.12407. Epub 2015 Feb 14.

  PMID: 25615282 BACKGROUND

• Dake MD, Van Alstine WG, Zhou Q, Ragheb AO. Polymer-free paclitaxel-coated Zilver PTX Stents--evaluation of pharmacokinetics and comparative safety in porcine arteries. J Vasc Interv Radiol. 2011 May;22(5):603-10. doi: 10.1016/j.jvir.2010.12.027. Epub 2011 Mar 17.

  PMID: 21419649 BACKGROUND

• Banerjee S, Sarode K, Mohammad A, Gigliotti O, Baig MS, Tsai S, Shammas NW, Prasad A, Abu-Fadel M, Klein A, Armstrong EJ, Jeon-Slaughter H, Brilakis ES, Bhatt DL. Femoropopliteal Artery Stent Thrombosis: Report From the Excellence in Peripheral Artery Disease Registry. Circ Cardiovasc Interv. 2016 Feb;9(2):e002730. doi: 10.1161/CIRCINTERVENTIONS.115.002730.

  PMID: 26839391 BACKGROUND

• Federman DG, Ladiiznski B, Dardik A, Kelly M, Shapshak D, Ueno CM, Mostow EN, Richmond NA, Hopf HW. Wound Healing Society 2014 update on guidelines for arterial ulcers. Wound Repair Regen. 2016 Jan-Feb;24(1):127-35. doi: 10.1111/wrr.12395. No abstract available.

  PMID: 26663663 BACKGROUND

• van Overhagen H, Nakamura M, Geraghty PJ, Rao S, Arroyo M, Soga Y, Iida O, Armstrong E, Nakama T, Fujihara M, Ansari MM, Mathews SJ, Goueffic Y, Jaff MR, Weinberg I, Pinto DS, Ohura N, Couch K, Mustapha JA. Primary results of the SAVAL randomized trial of a paclitaxel-eluting nitinol stent versus percutaneous transluminal angioplasty in infrapopliteal arteries. Vasc Med. 2023 Dec;28(6):571-580. doi: 10.1177/1358863X231199489. Epub 2023 Oct 16.

  PMID: 37844137 DERIVED

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Results Point of Contact

• Title: Dana Hromyak
• Organization: Boston Scientific

Dana.Hromyak@bsci.com

1 216-526-8534

Study Officials

• Jihad Mustapha, MD

  Advanced Cardiac & Vascular Centers for Amputation Prevention

  PRINCIPAL INVESTIGATOR

• Hendrik van Overhagen, MD

  HAGA Ziekenhuis (HagaZiekenhuis van Den Haag)

  PRINCIPAL INVESTIGATOR

• Patrick Geraghty, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Masato Nakamura, MD, PhD

  Toho University Ohashi Medical Center - Division of Cardiovascular Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A review of the wound assessment data will be completed by independent reviewer(s) who will be blinded to the randomized therapy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 201 subjects will be randomized in a 2:1 fashion for phase A RCT. Randomizations will be stratified by investigational center and lesion length with 2 subjects receiving the DES BTK for every 1 subject receiving treatment with standard PTA.

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: June 11, 2018
• Study Start: August 31, 2018
• Primary Completion: April 21, 2022
• Study Completion: December 20, 2023
• Last Updated: July 1, 2024
• Results First Posted: August 14, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); FR (4); BE (3); US (26); JP (8)