Sirolimus Coated BALloon Versus Standard Balloon Angioplasty in The Treatment of Below The Knee Arterial Disease

Official title

MAGICAL BTK: Randomized Controlled Trial of MAGIcTouch - Sirolimus Coated BALloon Versus Standard Balloon Angioplasty in The Treatment of Below The Knee Arterial Disease

Overview

This is a Pivotal, Prospective, randomized, two arm, placebo controlled, single-blind, multicenter trial that will be conducted at approximately 80 sites; approx. 50 sites with at least 50% of subjects will be recruited from USA and approx. 30 sites OUS - Europe, Australia and Asia. Each site will be capped at 30 maximum subjects recruited. The main goal of this clinical trial is to determine the effectiveness and safety of the sirolimus drug coated balloon (DCB) versus standard percutaneous transluminal angioplasty (PTA) for the treatment of below the knee arterial disease. Eligible subjects will be randomised in a 1:1 allocation ratio and stratified by recruiting countries. Each subject will be randomized to receive either: 1. MagicTouch PTA sirolimus coated balloon catheter (DCB) in addition to standard balloon angioplasty or 2. Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA).

Detailed description

The burden of limb loss because of peripheral arterial disease (PAD) is high and this problem is set to worsen globally. Treatment of PAD primarily involves revascularisation of the limb. Angioplasty as a first line strategy of revascularization over surgical procedures has been adopted by many vascular centres. In recent years, studies have shown that local drug delivery using drug coated balloons (DCB) during angioplasty for PAD can successfully deliver effective local tissue concentrations of antiproliferative drugs to the lesions in the artery involved in the PAD. This offers the potential for sustained anti-restenotic efficacy.

Randomized trials have shown superiority of Paclitaxel DCBs over just plain-balloon angioplasty for treatment of femoropopliteal occlusive disease, and DCB is now considered the standard of care in many regions. However, the efficacy of Paclitaxel below the knee is less clear, as multiple randomized trials evaluating Paclitaxel-coated DCBs below the knee have failed to meet their primary endpoints. Alternative drugs for DCBs are therefore needed and sirolimus may offer an attractive alternative. Compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high margin of safety. It has a high transfer rate to the vessel wall and has been shown to effectively inhibit neointimal hyperplasia in the porcine coronary model. In the coronary artery interventions, preliminary clinical studies using Sirolimus DCBs have also shown excellent procedural and 6- \& 12- months patency. This study aims to conduct a single blind, randomised controlled multicentre trial of sirolimus drug coated balloon versus standard percutaneous transluminal angioplasty in patients with below the knee arterial disease.

Interventions

• Device MagicTouch PTA Sirolimus drug coated balloon
  All patients must first be treated with pre dilatation with a standard balloon angioplasty using any standard balloon catheters at the discretion of the operator. Magic Touch PTA Sirolimus coated balloon catheter is an adjunct treatment that should be used in combination with standard balloon angioplasty. Following successful crossing of wire across the lesion and plain balloon angioplasty of arterial lesion with successful lesion preparation with residual lesion \<30%, subjects will be randomiz
• Device Placebo balloon angioplasty
  For participants randomized to a Placebo balloon angioplasty group, a Placebo balloon angioplasty in addition to standard balloon angioplasty will be performed.

Primary outcome measures

• Primary patency at 12 months defined as freedom from Target Vessel Occlusion, Binary Restenosis, Clinically-Driven Target Lesion Revascularization and Major Amputation. [Time frame: 12 months]
• Composite safety endpoint [Time frame: 6-months for n.1 and n.2; 30 days for n.3]

Secondary outcome measures (12)

• Secondary Safety endpoint 1 [Time frame: 1, 6, 12, 24, 36, 48 and 60 months]
• Secondary Safety endpoint 2 [Time frame: 1, 6, 12, 24, 36, 48 and 60 months]
• Secondary Safety endpoint 3 [Time frame: 1, 6, 12, 24, 36, 48 and 60 months]
• Secondary Safety endpoint 4 [Time frame: From day 0 to day 14]
• Secondary Safety endpoint 5 [Time frame: From day 0 to 60 months]
• Secondary efficacy endpoints 1 [Time frame: From day 0 to 60 months]
• Secondary efficacy endpoints 2 [Time frame: 6, 12, 24, and 36 months]
• Secondary efficacy endpoints 3 [Time frame: 6,12,24 and 36 months]
• Secondary efficacy endpoints 4 [Time frame: 24 months]
• Secondary efficacy endpoints 5 [Time frame: 6, 12 and 24 months]
• Secondary efficacy endpoints 6 [Time frame: 6, 12, 24, 36, 48 and 60 months]
• Secondary efficacy endpoints 7 [Time frame: 6,12, 24, 36, 48 and 60 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 21 years or minimum age (is allowed the inclusion of subjects > 21 years OR adulthood minimum age (depending on the US state regulations)
• Rutherford class 4 with documented WIFI score, not exceeding more than 30% of target patient population.
• Rutherford class 5 to 6 in the target limb with documented WIFI score.

Intraoperative Inclusion Criteria:

• Single or sequential de novo or re-stenotic lesions (stenosis of > 50% or occlusions) from 2 to 20cm in the proximal 200mm of below the knee arteries. Lesion is considered as one lesion if there is maximum of 30 mm gap between lesions at discretion of investigator. Below the knee arteries are Tibio-peroneal trunk, Peroneal bifurcation, anterior tibial artery, posterior tibial artery and peroneal artery. With documented Distal Run off a maximum of two tibial vessels can be treated in the index procedure. Inflow free from flow limiting lesions (<50% stenosis) confirmed by duplex or angiography. Subjects with flow limiting inflow lesions (>50% stenosis) can be included if lesion had been treated successfully (<30% residual stenosis) before or during the index procedure.
• Target vessel has angiographically documented unimpaired (<50% stenosis) run off into a named Tibio-pedal artery (Peroneal, Anterior Tibial/ Dorsalis Pedis/ Posterior Tibial Artery)

Exclusion criteria

• Comorbid conditions limiting life expectancy ≤ 1 year
• Subject is currently participating in another investigational drug or device study that has not reached first primary endpoint yet
• Subject is lactating, pregnant or planning to become pregnant during the course of the study
• Subject with extensive tissue loss salvageable only with complex foot reconstruction or non-traditional trans metatarsal amputation. This includes subjects with:

• Osteomyelitis including and/or proximal to the metatarsal head
• Gangrene involving the plantar skin of the forefoot, midfoot,or heel
• Deep ulcer or large shallow ulcer (> 3 cm) involving the plantar skin of the forefoot, midfoot, or heel
• Full thickness heel ulcer with/without calcaneal involvement
• Any wound with calcaneal bone involvement
• Wounds that are deemed to be neuropathic or non-ischemic in nature
• Wounds that would require flap coverage or complex wound management for large soft tissue defect
• Full thickness wounds on the dorsum of the foot with exposed tendon or bone
• Prior bypass surgery of target vessel
• Planned amputation of the target limb (major)
• Previously implanted stent in the target lesion
• Vulnerable or protected adults
• Bleeding diathesis or another disorder (i.e. gastrointestinal ulceration,etc) which would prevent the use of mandated antiplatelet agents
• Known allergy to sirolimus
• Subjects with severe (Stage 4) renal disease, defined eGFR < 30.

Intraoperative exclusion criteria:

• Failure to successfully cross the target lesion with a guide wire
• Target vessel has lesions extending beyond the ankle joint
• Failure to obtain <30% residual stenosis prior to randomization
• Lesions requiring treatment through retrograde access . Retrograde wire crossing is allowed but treatment must be performed from the antegrade approach.
• Use of commercially available DCBs, bare metal stents, drug eluting stents, specialty balloons or atherectomy devices at the target lesions. (Non-compliant balloons are not considered specialty balloons). For Inflow and non-target lesions all the approved devices are allowed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 29 centers

• Honor Health Research & Innovation Institute — Scottsdale
• Cedars-Sinai Medical Center — Los Angeles
• University of California Los Angeles — Los Angeles
• Clearwater Cardiovascular Consultants — Clearwater
• Baptist Hospital of Miami — Miami
• University of South Florida — Tampa
• Vascular Institute of the Midwest — Davenport
• Unity Point Health Des Moines — Des Moines
• … and 21 more centers

Publications

• Giacoppo D, Cassese S, Harada Y, Colleran R, Michel J, Fusaro M, Kastrati A, Byrne RA. Drug-Coated Balloon Versus Plain Balloon Angioplasty for the Treatment of Femoropopliteal Artery Disease: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials. JACC Cardiovasc Interv. 2016 Aug 22;9(16):1731-42. doi: 10.1016/j.jcin.2016.06.008. PMID 27539695
• Clever YP, Peters D, Calisse J, Bettink S, Berg MC, Sperling C, Stoever M, Cremers B, Kelsch B, Bohm M, Speck U, Scheller B. Novel Sirolimus-Coated Balloon Catheter: In Vivo Evaluation in a Porcine Coronary Model. Circ Cardiovasc Interv. 2016 Apr;9(4):e003543. doi: 10.1161/CIRCINTERVENTIONS.115.003543. PMID 27069105
• Verheye S, Vrolix M, Kumsars I, Erglis A, Sondore D, Agostoni P, Cornelis K, Janssens L, Maeng M, Slagboom T, Amoroso G, Jensen LO, Granada JF, Stella P. The SABRE Trial (Sirolimus Angioplasty Balloon for Coronary In-Stent Restenosis): Angiographic Results and 1-Year Clinical Outcomes. JACC Cardiovasc Interv. 2017 Oct 23;10(20):2029-2037. doi: 10.1016/j.jcin.2017.06.021. Epub 2017 Sep 27. PMID 28964764
• Patel A, Irani FG, Pua U, Tay KH, Chong TT, Leong S, Chan ES, Tan GWL, Burgmans MC, Zhuang KD, Quek LHH, Kwan J, Damodharan K, Gogna A, Tan BP, Too CW, Chan SXJM, Chng SP, Yuan W, Tan BS. Randomized Controlled Trial Comparing Drug-coated Balloon Angioplasty versus Conventional Balloon Angioplasty for Treating Below-the-Knee Arteries in Critical Limb Ischemia: The SINGA-PACLI Trial. Radiology. 2021 PMID 34227886
• Choke E, Tang TY, Peh E, Damodharan K, Cheng SC, Tay JS, Finn AV. MagicTouch PTA Sirolimus Coated Balloon for Femoropopliteal and Below the Knee Disease: Results From XTOSI Pilot Study Up To 12 Months. J Endovasc Ther. 2022 Oct;29(5):780-789. doi: 10.1177/15266028211064816. Epub 2021 Dec 15. PMID 34911383
• Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, Brodmann M, Pilger E, Zeller T, Krishnan P, Gammon R, Muller-Hulsbeck S, Nehler MR, Benenati JF, Scheinert D; LEVANT 2 Investigators. Trial of a Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease. N Engl J Med. 2015 Jul 9;373(2):145-53. doi: 10.1056/NEJMoa1406235. Epub 2015 Jun 24. PMID 26106946
• Steiner S, Willfort-Ehringer A, Sievert H, Geist V, Lichtenberg M, Del Giudice C, Sauguet A, Diaz-Cartelle J, Marx C, Strobel A, Schult I, Scheinert D; RANGER SFA Investigators. 12-Month Results From the First-in-Human Randomized Study of the Ranger Paclitaxel-Coated Balloon for Femoropopliteal Treatment. JACC Cardiovasc Interv. 2018 May 28;11(10):934-941. doi: 10.1016/j.jcin.2018.01.276. Epub 201 PMID 29730375
• Zeller T, Baumgartner I, Scheinert D, Brodmann M, Bosiers M, Micari A, Peeters P, Vermassen F, Landini M, Snead DB, Kent KC, Rocha-Singh KJ; IN.PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 2014 Oct 14;64(15): PMID 25301459

Identifiers

NCT: NCT06182397 · CM-US-R04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗