SirolimUs CoaTed Balloon for The TrEatment of Below The Knee Arterial 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 below the knee arterial disease.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥ 21 years or minimum age
2. Rutherford class 4 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 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
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. Target vessel has angiographically documented run off to the foot after treatment (ie. without significant stenosis)

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. Target vessel has lesions extending beyond the ankle joint
13. Failure to obtain \<30% residual stenosis in a pre-existing lesion
14. Lesions requiring retrograde access (SAFARI)
15. Highly calcified lesions (Contiguous calcification on both sides of the lesion)
16. Use of DCBs, drug eluting stent, specialty balloons or artherectomy devices during the index procedure. (Non-compliant balloons are not considered specialty balloons)