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

Not Applicable

Recruiting

• Conditions: Arterial Disease of Legs; Below-the-knee Obstruction; PAD - Peripheral Arterial Disease
• Interventions: Device: Placebo balloon angioplasty; Device: MagicTouch PTA Sirolimus drug coated balloon

• Registration Number: NCT06182397
• Lead Sponsor: Concept Medical Inc.

Brief Summary

This is a Pivotal, Prospective, randomised, two arm, placebo controlled, single-blind, multicentre trial that will be conducted at approximately 70 sites; approx. 40 sites with at least 50% of subjects will be recruited from USA and approx. 30 sites OUS - Singapore, Australia and Japan. Each site will be capped at 30 maximum subjects recruited.

The main goal of this clinical trial is to determine the effectiveness and safety of the sirolimus drug coated balloon (DCB) versus standard percutaneous transluminal angioplasty (PTA) for the treatment of below the knee arterial disease.

Eligible subjects will be randomised in a 1:1 allocation ratio and stratified by recruiting countries. Each subject will be randomized to receive either:

1. MagicTouch PTA sirolimus coated balloon catheter (DCB) in addition to standard balloon angioplasty or

2. Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA).

Detailed Description

The burden of limb loss because 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 many vascular centres. In recent years, studies have shown that local drug delivery using drug coated balloons (DCB) during angioplasty for PAD can successfully deliver effective local tissue concentrations of antiproliferative 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 femoropopliteal occlusive disease, and DCB is now considered the standard of care in many regions. However, the efficacy of Paclitaxel below the knee is less clear, as multiple randomized trials evaluating Paclitaxel-coated DCBs below the knee have failed to meet their primary endpoints. Alternative drugs for DCBs are therefore needed and sirolimus may offer 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- \& 12- months 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.

Study Timeline

• Study First Submitted: 2023-12-04
• Study First Submitted QC: 2023-12-13
• Study First Posted: 2023-12-26
• Study Start: 2025-01-16
• Status Verified: 2025-02
• Last Update Submitted: 2025-03-15
• Last Update Posted: 2025-03-19
• Primary Completion: 2026-12-01
• Study Completion: 2031-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 368

Inclusion Criteria

1. Age > 21 years or minimum age (is allowed the inclusion of subjects > 21 years OR adulthood minimum age (depending on the US state regulations)

2. Rutherford class 4 with documented WIFI score, not exceeding more than 30% of target patient population.

3. Rutherford class 5 to 6 in the target limb with documented WIFI score.

   Intraoperative Inclusion Criteria:

4. 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 30 mm gap between lesions at discretion of investigator. Below the knee arteries are Tibio-peroneal trunk, Peroneal bifurcation, anterior tibial artery, posterior tibial artery and peroneal artery. With documented Distal Run off a maximum of two tibial vessels can be treated in the index procedure. 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 unimpaired (<50% stenosis) run off into a named Tibio-pedal artery (Peroneal, Anterior Tibial/ Dorsalis Pedis/ Posterior Tibial Artery)

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 lactating, pregnant or planning to become pregnant during the course of the study

4. Subject with extensive tissue loss salvageable only with complex foot reconstruction or non-traditional trans metatarsal amputation. This includes subjects with:

   1. Osteomyelitis including and/or proximal to the metatarsal head
   2. Gangrene involving the plantar skin of the forefoot, midfoot,or heel
   3. Deep ulcer or large shallow ulcer (> 3 cm) involving the plantar skin of the forefoot, midfoot, or heel
   4. Full thickness heel ulcer with/without calcaneal involvement
   5. Any wound with calcaneal bone involvement
   6. Wounds that are deemed to be neuropathic or non-ischemic in nature
   7. Wounds that would require flap coverage or complex wound management for large soft tissue defect
   8. Full thickness wounds on the dorsum of the foot with exposed tendon or bone

5. Prior bypass surgery of target vessel

6. Planned amputation of the target limb (major)

7. Previously implanted stent in the target lesion

8. Vulnerable or protected adults

9. Bleeding diathesis or another disorder (i.e. gastrointestinal ulceration,etc) which would prevent the use of mandated antiplatelet agents

10. Known allergy to sirolimus

11. Patients with severe (Stage 4) renal disease, defined eGFR < 30%.

    Intraoperative exclusion criteria:

12. Failure to successfully cross the target lesion with a guide wire

13. Target vessel has lesions extending beyond the ankle joint

14. Failure to obtain <30% residual stenosis prior to randomization

15. Lesions requiring retrograde access . Retrograde wire crossing is allowed but treatment must be performed from the antegrade approach.

16. Use of DCBs, bare metal stents, drug eluting stents, specialty balloons or atherectomy devices at the target lesions. (Non-compliant balloons are not considered specialty balloons)

17. For Inflow lesions and non-target lesions all the approved devices are allowed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo balloon angioplasty	Placebo balloon angioplasty	Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA)
MagicTouch PTA sirolimus DCB	MagicTouch PTA Sirolimus drug coated balloon	MagicTouch PTA sirolimus drug coated balloon (DCB) in addition to standard balloon angioplasty

Primary Outcome Measures

Name	Time	Method
Composite safety endpoint	6-months for n.1 and n.2; 30 days for n.3	Proportion of subjects who experienced any of the following: 1. 6-month above ankle major amputation of the index limb,; 2. 6-month major re-intervention (i.e., angioplasty of target lesion, new bypass graft, jump/interposition graft, or thrombectomy or thrombolysis); 3. Perioperative (30 day) mortality.
Primary patency at 12 months defined as freedom from Target Vessel Occlusion, Binary Restenosis, Clinically-Driven Target Lesion Revascularization and Major Amputation.	12 months	Binary restenosis will be defined as the proportion of subjects with duplex ultrasonography-derived peak systolic velocity ratio of \> 2.0 with correlating factors. If the PSV at the reference area in the vessel is abnormal, the core laboratory will employ the following other criteria to diagnose a stenosis of \> 50%: * Monophasic/ low resistive waveforms (parvus tardus) at the stenotic area or distal to an acoustic shadow; * Post-stenotic turbulence distal to the stenosis, along with a decrease in peak systolic velocities Gray scale/ B-mode imaging demonstrates significant plaque with stenosis along with a focal increase in the absolute PSV value.; * Occlusion = Absence of color filling and spectral Doppler signal.

Secondary Outcome Measures

Name	Time	Method
Secondary Safety endpoint 3	1, 6, 12, 24, 36, 48 and 60 months	Proportion of subjects with major target limb amputation
Secondary Safety endpoint 4	From day 0 to day 14	Proportion of subjects with target vessel thrombosis
Secondary Safety endpoint 2	1, 6, 12, 24, 36, 48 and 60 months	Proportion of subjects with death by any cause
Secondary Safety endpoint 1	1, 6, 12, 24, 36, 48 and 60 months	Proportion of device and procedure related death
Secondary efficacy endpoints 1	From day 0 to 60 months	Proportion of subjects with acute procedural success
Secondary efficacy endpoints 4	24 months	Primary patency, defined as a composite of freedom from Target Vessel Occlusion, Binary Restenosis, Clinically Driven Target Lesion Revascularization and Major Amputation
Secondary efficacy endpoints 8	From day 0 to day 1	Proportion of subjects with technical success
Secondary efficacy endpoints 9	2,4,6,8,12,16, 20, 24 weeks and 48 weeks	Wound assessment. Follow-up will cease once wound completely heals as adjudicated by the core lab.
Secondary efficacy endpoints 10	6, 12 and 24 months	Mean change from baseline in Toe pressure and ABI assessment
Secondary Functional endpoints 1	6,12 and 24 months	Mean change from baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) health-related quality of life questionnaire's VAS score and utility index.; The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Secondary efficacy endpoints 2	6, 12, 24, and 36 months	Proportion of subjects who are free from clinically driven Target Lesion Revascularization (CD-TLR)
Secondary efficacy endpoints 3	6,12,24 and 36 months	Proportion of subjects who are free from Target Vessel Revascularization (TVR)
Secondary Safety endpoint 5	From day 0 to 60 months	Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure
Secondary efficacy endpoints 6	6, 12, 24, 36, 48 and 60 months	Amputation-free survival
Secondary efficacy endpoints 5	6, 12 and 24 months	Proportion of subjects with restenosis. Restenosis is defined by duplex ultrasonographyderived peak systolic velocity ratio of \>2.0 and \<4.0
Secondary efficacy endpoints 7	6,12, 24, 36, 48 and 60 months	Proportion of subjects with clinical success defined as Improvement of ≥1 category in Rutherford classification compared to the pre-procedure Rutherford classification)
Secondary Functional endpoints 2	6,12 and 24 months	Mean change from baseline in walking impairment questionnaire score. In the WIQ distance score, the degree of difficulty in the walking of specific distances is ranked on a 0 to 4 Likert scale, in which 0 represents the inability to walk the distance and 4 represents no difficulty. A Likert scale is an ordinal scale of consecutive, equidistant, numerical values (ie, 0 to 4).

Trial Locations

Locations (4)

Columbia University Irving Medical center/NYPH; 🇺🇸 New York, New York, United States

Vascular Institute of the Midwest; 🇺🇸 Davenport, Iowa, United States

Northwell Health Long Island Jewish Medical Center; 🇺🇸 Lake Success, New York, United States

The Mount Sinai Hospital; 🇺🇸 New York, New York, United States