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

Atherosclerosis Clinical Trial

— FUTURE-BTK  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04511247
• Other study ID #: FUTURE-BTK
• Status: Recruiting
• Phase: N/A
• Start date: August 15, 2020
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: Concept Medical Inc.
• Contact: Edward Choke
• Phone: +65 69302164
• Email: edward.choke.t.c[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 219
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arterial Disease of Legs
• Atherosclerosis
• Peripheral Arterial Disease
• Peripheral Artery Disease

Intervention

Device:
• MagicTouch PTA Sirolimus drug coated balloon
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.
• POBA balloon
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

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Centre	Seoul
Singapore	Khoo Teck Puat Hospital	Singapore
Singapore	National University Hospital	Singapore
Singapore	Ng Teng Fong General Hospital	Singapore
Singapore	Sengkang General Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	Taipei Tzuchi Hospital	New Taipei City
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Shin Kong Wu Ho-Su Memorial Hospital	Taipei City
Taiwan	Taipei Mackay Memorial Hospital	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan City

Sponsors (1)

Lead Sponsor	Collaborator
Concept Medical Inc.

Countries where clinical trial is conducted

Korea, Republic of,  Singapore,  Taiwan, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health-related quality of life	Mean change from baseline in EuroQol-5Dimensions (EQ-5D) health-related quality of life questionnaire score at 12 and 24 months. The score ranges from 0 to 1, and a higher score means a better outcome	12 and 24 months
Other	Walking impairment	Mean change from baseline in walking impairment questionnaire score at 12 and 24 months. The score ranges from 0% to 100% and a higher score means a better outcome	12 and 24 months
Primary	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	Device and procedure related deaths	Proportion of device and procedure related deaths	1,6,12 and 24 Months
Secondary	All-cause death	Proportion of subjects died by any-cause	1,6,12 and 24 Months
Secondary	Major target limb amputation	Proportion of subjects with major target limb amputation	6,12 and 24 Months
Secondary	Target vessel thrombosis	Proportion of subjects with target vessel thrombosis	From day 0 to day 14
Secondary	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
Secondary	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
Secondary	Procedural Success	Proportion of subjects with procedural success during hospital stay	From Day 1 to discharge up to maximum of 30 days
Secondary	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
Secondary	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
Secondary	Primary patency	Primary patency rate at 12 and 24 months	12 and 24 Months
Secondary	Restenosis	Proportion of subjects with restenosis	6, 12 and 24 Months
Secondary	Subjects who are free from MAE	Proportion of subjects who are free from MAE	6 Months
Secondary	Amputation-free survival	Amputation-free survival	6, 12 and 24 Months
Secondary	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
Secondary	Device success	Proportion of subjects with device success at day 1	Day 1
Secondary	Technical success	Proportion of subjects with technical success at day 1	Day 1
Secondary	Wound assessment (if any)	Wound assessment (if any)	1, 6, 12, 24 Months
Secondary	Toe Pressure or ABPI assessment	Toe Pressure or ABPI assessment	6, 12, 24 Months