SirolimUs CoaTed Balloon for The TrEatment of Below The Knee Arterial Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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FUTURE BTK: Randomized Controlled Trial of First SirolimUs CoaTed Balloon VersUs StandaRd Balloon Angioplasty in The TrEatment of Below The Knee Arterial Disease

Conditions
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Peripheral Artery Disease, Atherosclerosis, Arterial Disease of Legs

Intervention / Treatment
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* Device: MagicTouch PTA Sirolimus drug coated balloon
* Device: POBA balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21 years or minimum age Rutherford class 4 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 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 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 run off to the foot after treatment (ie. without significant stenosis) 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). Target vessel has lesions extending beyond the ankle joint Failure to obtain <30% residual stenosis in a pre-existing lesion Lesions requiring retrograde access (SAFARI) Highly calcified lesions (Contiguous calcification on both sides of the lesion) Use of DCBs, drug eluting stent, specialty balloons or artherectomy devices during the index procedure. (Non-compliant balloons are not considered specialty balloons)

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible subjects will be randomised via a secure online system to a labelled device and to receive either Magic Touch sirolimus drug coated balloon in addition to standard balloon angioplasty or standard balloon angioplasty and placebo balloon.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MagicTouch PTA sirolimus drug coated balloon (DCB)<br>MagicTouch PTA sirolimus drug coated balloon (DCB) in addition to standard balloon angioplasty | Device: MagicTouch PTA Sirolimus drug coated balloon<br>* 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 sirolimus coated balloon will be applied at the lesion after appropriate sizing using the diameter of the plain balloon angioplasty.<br>|
| Active Comparator: Placebo balloon angioplasty<br>Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA) | Device: POBA balloon<br>* 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<br>|

What is the study measuring?
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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 deaths | Proportion of device and procedure related deaths | 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 subjects with major target limb amputation | 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAD, DCB, PTA, Sirolimus