Sirolimus Coated Balloon Versus Standard Balloon for SFA and Popliteal Artery Disease (FUTURE-SFA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerosis; Peripheral Artery Disease; Arterial Disease
• Intervention / Treatment: Device: MagicTouch PTA sirolimus drug coated balloon (DCB); Device: POBA standard balloon

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.

• Study Type: Interventional
• Enrollment (Estimated): 279
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edward Choke; Phone Number: +65 69302164; Email: edward.choke.t.c@singhealth.com.sg

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Asan Medical Centre
    • Contact: Lee Seung Hwan, Dr.
• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital
    • Contact: Jackie Ho
  • Singapore, Singapore
    • Recruiting
    • Singapore General Hospital
    • Contact: Tang Tjun Yip
  • Singapore, Singapore
    • Not yet recruiting
    • Ng Teng Fong General Hospital
    • Contact: Vikram Vijayan
  • Singapore, Singapore
    • Recruiting
    • Sengkang General Hospital
    • Contact: Edward Choke
  • Singapore, Singapore
    • Recruiting
    • Tan Tock Seng Hospital
    • Contact: Pua Uei, Dr.
  • Singapore, Singapore
    • Recruiting
    • Khoo Teck Puat Hospital
    • Contact: Leong Chuo Ren
• Taiwan
  • New Taipei City, Taiwan
    • Not yet recruiting
    • Far Eastern Memorial Hospital
    • Contact: Chen Jer-Shen
  • New Taipei City, Taiwan
    • Not yet recruiting
    • Taipei TzuChi Hospital
    • Contact: Huang Hsuan-Li, Dr.
  • Taipei City, Taiwan
    • Not yet recruiting
    • National Taiwan University Hospital
    • Contact: Lee Jen-Kuang, Dr.
  • Taipei City, Taiwan
    • Not yet recruiting
    • Shin Kong Wu Ho-Su Memorial Hospital
    • Contact: Lin Chia-Hsun
  • Taipei City, Taiwan
    • Not yet recruiting
    • Taipei Mackay Memorial Hospital
    • Contact: Tsai Cheng-Ting, Dr.
  • Taoyuan City, Taiwan
    • Not yet recruiting
    • Linkou Chang Gung Memorial Hospital
    • Contact: Chen Chun-Chi, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 21 years or minimum age

2. Rutherford class 3 to 6 in the target limb

   Intraoperative Inclusion Criteria

3. 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
4. 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.
5. At least one non-occluded crural vessel (ie. without significant stenosis) with angiographically documented run off to the foot.

Exclusion Criteria:

1. Comorbid conditions limiting life expectancy ≤ 1 year
2. Subject is currently participating in another investigational drug or device study that has not reached first primary endpoint yet
3. Subject is pregnant or planning to become pregnant during the course of the study
4. Heel gangrene
5. Prior bypass surgery of target vessel
6. Planned amputation of the target limb
7. Previously implanted stent in the target lesion
8. Vulnerable or protected adults
9. Bleeding diathesis or another disorder such as gastrointestinal ulceration which restrict the use of clopidogrel or aspirin

10. Known allergy to sirolimus

    Intraoperative Exclusion Criteria

11. 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)
12. Failure to obtain <30% residual stenosis in a pre-existing lesion
13. Highly calcific lesions
14. Use of DCBs, drug eluting stent, specialty balloons or artherectomy devices during the index procedure. (Non-compliant balloons are not considered specialty balloons)
15. Lesions requiring retrograde access (SAFARI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MagicTouch PTA sirolimus drug coated balloon (DCB); MagicTouch PTA sirolimus drug coated balloon (DCB) in addition to standard balloon angioplasty	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.
Active Comparator: Placebo balloon angioplasty; Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA)	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary patency at 6 months	Primary patency rate at 6 months defined as proportion of subjects with duplex ultrasonography-derived peak systolic velocity ratio of < 2.4 (in absence of target lesion revascularisation)	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device and procedure related death	Proportion of device and procedure related death	1, 6, 12 and 24 Months
All-cause death	Proportion of subjects died by any cause	1, 6, 12 and 24 Months
Major target limb amputation	Proportion of major target limb amputation	1, 6, 12 and 24 Months
Target vessel thrombosis	Proportion of subjects with target vessel thrombosis	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	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	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	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	From Day 0 to 24 Months Follow-up
Procedural Success	Proportion of subjects with procedural success during hospital stay	From Day 1 to discharge up to maximum of 30 days
Proportion of subjects who are free from clinically-driven Target Lesion Revascularization (TLR)	Proportion of subjects who are free from clinically-driven TLR	6,12 and 24 Months
Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR)	Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR)	6,12 and 24 Months
Primary patency	Primary patency rate at 12 and 24 months	12 and 24 Months
Restenosis	Proportion of subjects with restenosis	6, 12 and 24 Months
Subjects who are free from MAE	Proportion of subjects who are free from MAE	6 Months
Amputation-free survival	Amputation-free survival	6, 12 and 24 Months
Clinical Success	Proportion of subjects with clinical Success at 6, 12 and 24 months, Clinical success is defined as Improvement in Rutherford classification compared to the pre-procedure Rutherford classification	6, 12 and 24 Months
Device success	Proportion of subjects with device success at day 1	Day 1
Technical success	Proportion of subjects with technical success at day 1	Day 1
Wound assessment (if any)	Wound assessment (if any)	1, 6, 12, 24 Months
Toe Pressure or ABPI assessment	Toe Pressure or ABPI assessment	6, 12, 24 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of quality of life	Mean change from baseline in EuroQol-5Dimensions (EQ-5D) health-related quality of life questionnaire score at 12 and 24 months. The score ranges from 0 to 1, and a higher score means a better outcome	12 and 24 months
Walking impairment	Mean change from baseline in walking impairment questionnaire score at 12 and 24 months. The score ranges form 0% t 100%, and a higher score means a better outcome	12 and 24 months

Collaborators and Investigators

• Sponsor: Concept Medical Inc.
• Investigators: Principal Investigator: Edward Choke, Sengkang General Hospital

Publications and helpful links

General 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: PAD; Sirolimus; DCB; PTA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Atherosclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: FUTURE SFA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No