SirolimUs CoaTed Balloon for The TrEatment of Below The Knee Arterial Disease
- Conditions
- Peripheral Artery DiseaseAtherosclerosisArterial Disease of Legs
- Interventions
- Device: MagicTouch PTA Sirolimus drug coated balloonDevice: POBA balloon
- Registration Number
- NCT04511247
- 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 below the knee 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 219
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Age ≥ 21 years or minimum age
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Rutherford class 4 to 6 in the target limb
Intraoperative Inclusion Criteria
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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 30mm gap between lesions at discretion of investigator. Below the knee arteries are tibioperoneal trunk, anterior tibial artery, posterior tibial artery and peroneal artery
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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.
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Target vessel has angiographically documented run off to the foot after treatment (ie. without significant stenosis)
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Comorbid conditions limiting life expectancy ≤ 1 year
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Subject is currently participating in another investigational drug or device study that has not reached first primary endpoint yet
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Subject is pregnant or planning to become pregnant during the course of the study
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Heel gangrene
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Prior bypass surgery of target vessel
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Planned amputation of the target limb
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Previously implanted stent in the target lesion
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Vulnerable or protected adults
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Bleeding diathesis or another disorder such as gastrointestinal ulceration which restrict the use of clopidogrel or aspirin
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Known allergy to sirolimus
Intraoperative Exclusion Criteria
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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).
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Target vessel has lesions extending beyond the ankle joint
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Failure to obtain <30% residual stenosis in a pre-existing lesion
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Lesions requiring retrograde access (SAFARI)
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Highly calcified lesions (Contiguous calcification on both sides of the lesion)
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Use of DCBs, drug eluting stent, specialty balloons or artherectomy devices during the index procedure. (Non-compliant balloons are not considered specialty balloons)
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 MagicTouch PTA sirolimus drug coated balloon (DCB) in addition to standard balloon angioplasty Placebo balloon angioplasty POBA 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 Primary patency 12 and 24 Months Primary patency rate at 12 and 24 months
All-cause death 1,6,12 and 24 Months Proportion of subjects died by any-cause
Major target limb amputation 6,12 and 24 Months Proportion of subjects with major target limb amputation
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.
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
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 Lesion Revascularization (TLR) 6,12 and 24 Months Proportion of subjects who are free from clinically-driven TLR
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)
Restenosis 6, 12 and 24 Months Proportion of subjects with restenosis
Subjects who are free from MAE 6 Months Proportion of subjects who are free from MAE
Amputation-free survival 6, 12 and 24 Months Amputation-free survival
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
Technical success Day 1 Proportion of subjects with technical success at day 1
Device and procedure related deaths 1,6,12 and 24 Months Proportion of device and procedure related deaths
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
Trial Locations
- Locations (13)
Taipei Mackay Memorial Hospital
🇨🇳Taipei City, Taiwan
Sengkang General Hospital
🇸🇬Singapore, Singapore
Ng Teng Fong General Hospital
🇸🇬Singapore, Singapore
Far Eastern Memorial Hospital
🇨🇳New Taipei City, Taiwan
National University Hospital
🇸🇬Singapore, Singapore
Asan Medical Centre
🇰🇷Seoul, Korea, Republic of
Singapore General Hospital
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan City, Taiwan
Khoo Teck Puat Hospital
🇸🇬Singapore, Singapore
Taipei Tzuchi Hospital
🇨🇳New Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Shin Kong Wu Ho-Su Memorial Hospital
🇨🇳Taipei City, Taiwan