Sirolimus Coated Balloon Versus Standard Balloon for SFA and Popliteal Artery Disease

Official title

Randomized Controlled Trial of First Sirolimus Coated Balloon Versus Standard Balloon Angioplasty in The Treatment of Superficial Femoral Artery and Popliteal Artery Disease

Overview

This study aims to conduct a randomized, double blind, randomised controlled multicentre trial of sirolimus drug coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial and popliteal arterial disease.

Detailed description

The burden of limb loss as a result 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 most vascular centers. Local drug delivery using drug coated balloons (DCB) during angioplasty for PAD can successfully deliver effective local tissue concentrations of anti-proliferative 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 PAD, and DCB is now considered the standard of care. However a recent meta-analyses which showed increased mortality at two years in patients treated with paclitaxel DCBs have called into question the safety of paclitaxel based DCBs.

Alternative drugs for DCBs are therefore urgently needed and sirolimus offers 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 month patency.

Interventions

• Device MagicTouch PTA sirolimus drug coated balloon (DCB)
  For participants randomised to MagicTouch PTA sirolimus DCB, following successful plain balloon angioplasty of the arterial lesion, (defined as \<30% residual stenosis after treatment at rated burst pressure of the angioplasty balloon), MagicTouch PTA sirolimus coated balloon will be applied at the lesion after appropriate sizing using the diameter of the plain balloon angioplasty.
• Device POBA standard balloon
  For participants randomised to the standard balloon angioplasty group, a placebo standard balloon which is identical to the SCB will also be applied at the lesion after appropriate sizing using the diameter of the plain balloon angioplasty.

Primary outcome measures

• Primary patency at 6 months [Time frame: 6 Months]

Secondary outcome measures (12)

• Device and procedure related death [Time frame: 1, 6, 12 and 24 Months]
• All-cause death [Time frame: 1, 6, 12 and 24 Months]
• Major target limb amputation [Time frame: 1, 6, 12 and 24 Months]
• Target vessel thrombosis [Time frame: From day 0 to day 14]
• Proportion of subjects who experienced either death at 6 month or major target limb amputation at 6 month or target vessel thrombosis within 14 days [Time frame: Day 0 to day 14, 6 Months]
• Occurrence of adverse events (AEs), serious AEs and AEs related to device and Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure [Time frame: From Day 0 to 24 Months Follow-up]
• Procedural Success [Time frame: From Day 1 to discharge up to maximum of 30 days]
• Proportion of subjects who are free from clinically-driven Target Lesion Revascularization (TLR) [Time frame: 6,12 and 24 Months]
• Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR) [Time frame: 6,12 and 24 Months]
• Primary patency [Time frame: 12 and 24 Months]
• Restenosis [Time frame: 6, 12 and 24 Months]
• Subjects who are free from MAE [Time frame: 6 Months]

Eligibility criteria

Inclusion criteria

• Age ≥ 21 years or minimum age
• Rutherford class 3 to 6 in the target limb

Intraoperative Inclusion Criteria

• Single or sequential de novo or re-stenotic lesions (stenosis of > 50% or occlusions) from 2 to 20cm in the femoropopliteal arteries. Lesion is considered as one lesion if there is maximum of 30mm gap between lesions at discretion of investigator. Femoropopliteal arteries are superficial femoral artery, popliteal artery P1 and P2
• 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.
• At least one non-occluded crural vessel (ie. without significant stenosis) with angiographically documented run off to the foot.

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 pregnant or planning to become pregnant during the course of the study
• Heel gangrene
• Prior bypass surgery of target vessel
• Planned amputation of the target limb
• Previously implanted stent in the target lesion
• Vulnerable or protected adults
• Bleeding diathesis or another disorder such as gastrointestinal ulceration which restrict the use of clopidogrel or aspirin
• Known allergy to sirolimus

Intraoperative Exclusion Criteria

• Failure to successfully cross the target lesion with a guide wire (successful crossing means tip of the guide wire distal to the target lesion in the absence of flow limiting dissections or perforations)
• Failure to obtain <30% residual stenosis in a pre-existing lesion
• Highly calcific lesions
• Use of DCBs, drug eluting stent, specialty balloons or artherectomy devices during the index procedure. (Non-compliant balloons are not considered specialty balloons)
• Lesions requiring retrograde access (SAFARI)

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

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 8 centers

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• Kaoshiung Chang Gung Memorial Hospital — Kaohsiung City
• Far Eastern Memorial Hospital — New Taipei City
• Taipei Tzuchi Hospital — New Taipei City
• China Medical University Hospital — Taichung
• National Taiwan University Hospital — Taipei
• Shin Kong Wu Ho-Su Memorial Hospital — Taipei
• Linkou Chang Gung Memorial Hospital — Taoyuan City

Singapore · 6 centers

• Khoo Teck Puat Hospital — Singapore
• National University Hospital — Singapore
• Ng Teng Fong General Hospital — Singapore
• Sengkang General Hospital — Singapore
• Singapore General Hospital — Singapore
• Tan Tock Seng Hospital — Singapore

Thailand · 6 centers

• Phramongkutklao Hospital — Bangkok
• Rajavithi Hospital — Bangkok
• Ramathibodi Hospital — Bangkok
• Siriraj Hospital — Bangkok
• Vajira Hospital — Bangkok
• Thammasat University Hospital — Pathum Thani

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

Identifiers

NCT: NCT04511234 · FUTURE SFA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗