Clinical trial NCT04511247: SirolimUs CoaTed Balloon for The TrEatment of Below The Knee Arterial Disease
Official title: FUTURE BTK: Randomized Controlled Trial of First SirolimUs CoaTed Balloon VersUs StandaRd Balloon Angioplasty in The TrEatment of Below The Knee Arterial Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Artery Disease
Atherosclerosis
Arterial Disease of Legs
Keywords: PAD
DCB
PTA
Sirolimus
Lead sponsor: Concept Medical Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-13
Enrollment: 219
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Primary patency at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Device and procedure related deaths
timeFrame: 1,6,12 and 24 Months
measure: All-cause death
timeFrame: 1,6,12 and 24 Months
measure: Major target limb amputation
timeFrame: 6,12 and 24 Months
measure: Target vessel thrombosis
timeFrame: From day 0 to day 14
measure: 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.
timeFrame: Day 0 to day 14, 6 Months
measure: Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure
timeFrame: From Day 0 to 24 Months Follow-up
measure: Procedural Success
timeFrame: From Day 1 to discharge up to maximum of 30 days
measure: Proportion of subjects who are free from clinically-driven Target Lesion Revascularization (TLR)
timeFrame: 6,12 and 24 Months
measure: Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR)
timeFrame: 6,12 and 24 Months
measure: Primary patency
timeFrame: 12 and 24 Months
measure: Restenosis
timeFrame: 6, 12 and 24 Months
measure: Subjects who are free from MAE
timeFrame: 6 Months
measure: Amputation-free survival
timeFrame: 6, 12 and 24 Months
measure: Clinical Success
timeFrame: 6, 12 and 24 Months
measure: Device success
timeFrame: Day 1
measure: Technical success
timeFrame: Day 1
measure: Wound assessment (if any)
timeFrame: 1, 6, 12, 24 Months
measure: Toe Pressure or ABPI assessment
timeFrame: 6, 12, 24 Months
Other outcomes:
measure: Health-related quality of life
timeFrame: 12 and 24 months
measure: Walking impairment
timeFrame: 12 and 24 months
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Centre
city: Singapore
country: Singapore
facility: Khoo Teck Puat Hospital
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Ng Teng Fong General Hospital
city: Singapore
country: Singapore
facility: Sengkang General Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Tzuchi Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Shin Kong Wu Ho-Su Memorial Hospital
city: Taipei City
country: Taiwan
facility: Taipei Mackay Memorial Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Sengkang General Hospital
name: Edward Choke
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giacoppo D, Cassese S, Harada Y, Colleran R, Michel J, Fusaro M, Kastrati A, Byrne RA. Drug-Coated Balloon Versus Plain Balloon Angioplasty for the Treatment of Femoropopliteal Artery Disease: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials. JACC Cardiovasc Interv. 2016 Aug 22;9(16):1731-42. doi: 10.1016/j.jcin.2016.06.008.
citation: Clever YP, Peters D, Calisse J, Bettink S, Berg MC, Sperling C, Stoever M, Cremers B, Kelsch B, Bohm M, Speck U, Scheller B. Novel Sirolimus-Coated Balloon Catheter: In Vivo Evaluation in a Porcine Coronary Model. Circ Cardiovasc Interv. 2016 Apr;9(4):e003543. doi: 10.1161/CIRCINTERVENTIONS.115.003543.
citation: Verheye S, Vrolix M, Kumsars I, Erglis A, Sondore D, Agostoni P, Cornelis K, Janssens L, Maeng M, Slagboom T, Amoroso G, Jensen LO, Granada JF, Stella P. The SABRE Trial (Sirolimus Angioplasty Balloon for Coronary In-Stent Restenosis): Angiographic Results and 1-Year Clinical Outcomes. JACC Cardiovasc Interv. 2017 Oct 23;10(20):2029-2037. doi: 10.1016/j.jcin.2017.06.021. Epub 2017 Sep 27.