Sirolimus Coated BALloon Versus Standard Balloon Angioplasty in The Treatment of Below The Knee Arterial Disease

Study Overview
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Brief Summary
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This is a randomised, placebo-controlled, single blind, multicentre trial. The main goal of this clinical trial is to determine the effectiveness (primary patency) and safety of the sirolimus DCB versus standard PTA for the treatment of below the knee arterial disease. Participants will be randomized to receive either: MagicTouch PTA sirolimus coated balloon catheter (DCB) in addition to standard balloon angioplasty or Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA).

Detailed Description
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The burden of limb loss as a result of a peripheral arterial disease (PAD) is high and this problem is set to worsen globally. Treatment of PAD primarily involves revascularisation of the limb and a lot of vascular centers adopted angioplasty as a first line strategy of revascularisation over surgical procedures. Local drug delivery using 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. 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, the safety of paclitaxel based DCBs has been called into question by recent meta-analyses, so alternative drugs for DCBs are 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. This study aims to conduct a single blind, randomised, controlled, multicentre trial of sirolimus drug coated balloon versus standard percutaneous transluminal angioplasty in patients with below the knee arterial disease.

Official Title
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Randomized Controlled Trial of MAGIcTouch - Sirolimus Coated BALloon Versus Standard Balloon Angioplasty in The Treatment of Below The Knee Arterial Disease

Conditions
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Arterial Disease of Legs

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


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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MagicTouch PTA sirolimus 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>|
| Placebo Comparator: Placebo balloon angioplasty<br>Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA) | Device: Placebo balloon angioplasty<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 rate after the index procedure | The proportion of subjects with duplex ultrasonography-derived peak systolic velocity ratio of ≤2.4 (in absence of any target lesion revascularisation). | 6 months | 
| Composite safety endpoint | Proportion of subjects who experienced any of the following: ankle amputation of the index limb major re-intervention (i.e. angioplasty of target lesion, new bypass graft, jump/interposition graft, or thrombectomy or thrombolysis) Perioperative mortality | 6-months for n.1 and n.2; 30 days for n.3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of device related death | Proportion of device related death | 1, 6, 12, 24, 36, 48 and 60 months | 
| Proportion of procedure related death | Proportion of procedure related death | 1, 6, 12, 24, 36, 48 and 60 months | 
| Proportion of subjects died | Proportion of subjects died by any cause | 1, 6, 12, 24, 36, 48 and 60 months | 
| Proportion of subjects with major target limb amputation | Proportion of subjects with major target limb amputation | 1, 6, 12, 24, 36, 48 and 60 months | 
| Proportion of subjects with target vessel thrombosis | Proportion of subjects with target vessel thrombosis | From day 0 to day 14 | 
| Proportion of subjects who experienced any of the following event | Proportion of subjects who experienced any of the following event: death major target limb amputation target vessel thrombosis | 6-months for n.1 and n.2; From day 0 to day 14 for n.3 | 
| Occurrence of AEs, SAEs and AEs related to device and procedure | Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure | from o to 60 months | 
| subjects free from TLR | Proportion of subjects who are free from TLR | 6,12,24 and 36 months | 
| subjects free from TVR | Proportion of subjects who are free from TVR | 6,12,24 and 36 months | 
| Primary patency rate | Primary patency rate | 12 and 24 months | 
| Proportion of subjects with restenosis | Proportion of subjects with restenosis, defined by duplex ultrasonography-derived peak systolic velocity ratio of < 2.0 and <4.0 | 6,12 and 24 months | 
| Amputation-free survival | Amputation-free survival | 6,12,24,36,48 and 60 months | 
| Proportion of subjects with clinical success | Proportion of subjects with clinical success, defined as Improvement in Rutherford classification compared to the pre-procedure Rutherford classification | 6,12,24,36,48 and 60 months | 
| Proportion of subjects with device success | Proportion of subjects with device success | From day 0 to day 1 | 
| Proportion of subjects with technical success | Proportion of subjects with technical success | From day 0 to day 1 | 
| Mean change from baseline in ABI assessment | Mean change from baseline in ABI assessment | 6,12 and 24 months | 
| Mean change from baseline in Toe pressure | Mean change from baseline in Toe pressure | 6,12 and 24 months | 
| Mean change from baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) | Mean change from baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) | 12 and 24 months | 
| Mean change from baseline in walking impairment questionnaire score | Mean change from baseline in walking impairment questionnaire score | 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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below the knee, PTA, Angioplasty, lower limb