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

Not Applicable

Recruiting

• Conditions: Peripheral Artery Disease; Arterial Disease; Atherosclerosis
• Interventions: Device: MagicTouch PTA sirolimus drug coated balloon (DCB); Device: POBA standard balloon

• Registration Number: NCT04511234
• Lead Sponsor: Concept Medical Inc.

Brief Summary

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.

Study Timeline

• Study First Submitted: 2020-08-05
• Study First Submitted QC: 2020-08-10
• Study First Posted: 2020-08-13
• Study Start: 2020-09-08
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-06
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 279

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MagicTouch PTA sirolimus drug coated balloon (DCB)	MagicTouch PTA sirolimus drug coated balloon (DCB)	MagicTouch PTA sirolimus drug coated balloon (DCB) in addition to standard balloon angioplasty
Placebo balloon angioplasty	POBA standard balloon	Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA)

Primary Outcome Measures

Name	Time	Method
Primary patency at 6 months	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)

Secondary Outcome Measures

Name	Time	Method
Amputation-free survival	6, 12 and 24 Months	Amputation-free survival
Device and procedure related death	1, 6, 12 and 24 Months	Proportion of device and procedure related death
Proportion of subjects who are free from clinically-driven Target Lesion Revascularization (TLR)	6,12 and 24 Months	Proportion of subjects who are free from clinically-driven TLR
Subjects who are free from MAE	6 Months	Proportion of subjects who are free from MAE
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	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
All-cause death	1, 6, 12 and 24 Months	Proportion of subjects died by any cause
Major target limb amputation	1, 6, 12 and 24 Months	Proportion of major target limb amputation
Procedural Success	From Day 1 to discharge up to maximum of 30 days	Proportion of subjects with procedural success during hospital stay
Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR)	6,12 and 24 Months	Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR)
Primary patency	12 and 24 Months	Primary patency rate at 12 and 24 months
Restenosis	6, 12 and 24 Months	Proportion of subjects with restenosis
Clinical Success	6, 12 and 24 Months	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
Device success	Day 1	Proportion of subjects with device success at day 1
Target vessel thrombosis	From day 0 to day 14	Proportion of subjects with target vessel thrombosis
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	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
Wound assessment (if any)	1, 6, 12, 24 Months	Wound assessment (if any)
Toe Pressure or ABPI assessment	6, 12, 24 Months	Toe Pressure or ABPI assessment
Technical success	Day 1	Proportion of subjects with technical success at day 1

Trial Locations

Locations (13)

Asan Medical Centre; 🇰🇷 Seoul, Korea, Republic of

Khoo Teck Puat Hospital; 🇸🇬 Singapore, Singapore

National University Hospital; 🇸🇬 Singapore, Singapore

Singapore General Hospital; 🇸🇬 Singapore, Singapore

Ng Teng Fong General Hospital; 🇸🇬 Singapore, Singapore

Sengkang General Hospital; 🇸🇬 Singapore, Singapore

Tan Tock Seng Hospital; 🇸🇬 Singapore, Singapore

Taipei Tzuchi Hospital; 🇨🇳 New Taipei City, Taiwan

Taipei Mackay Memorial Hospital; 🇨🇳 Taipei City, Taiwan

Linkou Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taiwan

Far Eastern Memorial Hospital; 🇨🇳 New Taipei City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan

Shin Kong Wu Ho-Su Memorial Hospital; 🇨🇳 Taipei City, Taiwan