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

Arterial Disease of Legs Clinical Trial

— MAGICAL BTK  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06182397
• Other study ID #: CM-US-R04
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: February 1, 2031

Study information

• Verified date: June 2024
• Source: Concept Medical Inc.
• Contact: Farhana Siddique
• Phone: +919725495366
• Email: farhana[@]conceptmedical.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 368
• Est. completion date: February 1, 2031
• Est. primary completion date: December 1, 2026
• 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 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 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.

Related Conditions & MeSH terms

• Arterial Disease of Legs

Intervention

Device:
• MagicTouch PTA Sirolimus drug coated balloon
All patients must first be treated with pre dilatation with a standard balloon angioplasty using any standard balloon catheters at the discretion of the operator. Magic Touch PTA Sirolimus coated balloon catheter is an adjunct treatment that should be used in combination with standard balloon angioplasty. Following successful crossing of wire across the lesion and plain balloon angioplasty of arterial lesion with successful lesion preparation with residual lesion <30%, subjects will be randomized to receive study device balloon. If patients are assigned to MagicTouch PTA Sirolimus DCB, the Angioplasty of lower limb will be performed with this device in addition to standard balloon angioplasty.
• Placebo balloon angioplasty
For participants randomized to a Placebo balloon angioplasty group, a Placebo balloon angioplasty in addition to standard balloon angioplasty will be performed.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Concept Medical Inc.

References & Publications (9)

Choke E, Tang TY, Peh E, Damodharan K, Cheng SC, Tay JS, Finn AV. MagicTouch PTA Sirolimus Coated Balloon for Femoropopliteal and Below the Knee Disease: Results From XTOSI Pilot Study Up To 12 Months. J Endovasc Ther. 2022 Oct;29(5):780-789. doi: 10.1177 — View 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):e00 — 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 C — View Citation

Mustapha JA, Brodmann M, Geraghty PJ, Saab F, Settlage RA, Jaff MR; Lutonix BTK Study Investigators. Drug-Coated vs Uncoated Percutaneous Transluminal Angioplasty in Infrapopliteal Arteries: Six-Month Results of the Lutonix BTK Trial. J Invasive Cardiol. — View Citation

Patel A, Irani FG, Pua U, Tay KH, Chong TT, Leong S, Chan ES, Tan GWL, Burgmans MC, Zhuang KD, Quek LHH, Kwan J, Damodharan K, Gogna A, Tan BP, Too CW, Chan SXJM, Chng SP, Yuan W, Tan BS. Randomized Controlled Trial Comparing Drug-coated Balloon Angioplas — View Citation

Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, Brodmann M, Pilger E, Zeller T, Krishnan P, Gammon R, Muller-Hulsbeck S, Nehler MR, Benenati JF, Scheinert D; LEVANT 2 Investigators. Trial of a Paclitaxel-Coated Balloon for Femo — View Citation

Steiner S, Willfort-Ehringer A, Sievert H, Geist V, Lichtenberg M, Del Giudice C, Sauguet A, Diaz-Cartelle J, Marx C, Strobel A, Schult I, Scheinert D; RANGER SFA Investigators. 12-Month Results From the First-in-Human Randomized Study of the Ranger Pacli — 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 Result — View Citation

Zeller T, Baumgartner I, Scheinert D, Brodmann M, Bosiers M, Micari A, Peeters P, Vermassen F, Landini M, Snead DB, Kent KC, Rocha-Singh KJ; IN.PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arte — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary patency at 12 months defined as freedom from Target Vessel Occlusion, Binary Restenosis, Clinically-Driven Target Lesion Revascularization and Major Amputation.	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.	12 months
Primary	Composite safety endpoint	Proportion of subjects who experienced any of the following: 6-month above ankle major amputation of the index limb,; 6-month major re-intervention (i.e., angioplasty of target lesion, new bypass graft, jump/interposition graft, or thrombectomy or thrombolysis); Perioperative (30 day) mortality.	6-months for n.1 and n.2; 30 days for n.3
Secondary	Secondary Safety endpoint 1	Proportion of device and procedure related death	1, 6, 12, 24, 36, 48 and 60 months
Secondary	Secondary Safety endpoint 2	Proportion of subjects with death by any cause	1, 6, 12, 24, 36, 48 and 60 months
Secondary	Secondary Safety endpoint 3	Proportion of subjects with major target limb amputation	1, 6, 12, 24, 36, 48 and 60 months
Secondary	Secondary Safety endpoint 4	Proportion of subjects with target vessel thrombosis	From day 0 to day 14
Secondary	Secondary Safety endpoint 5	Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure	From day 0 to 60 months
Secondary	Secondary efficacy endpoints 1	Proportion of subjects with acute procedural success	From day 0 to 60 months
Secondary	Secondary efficacy endpoints 2	Proportion of subjects who are free from clinically driven Target Lesion Revascularization (CD-TLR)	6, 12, 24, and 36 months
Secondary	Secondary efficacy endpoints 3	Proportion of subjects who are free from Target Vessel Revascularization (TVR)	6,12,24 and 36 months
Secondary	Secondary efficacy endpoints 4	Primary patency, defined as a composite of freedom from Target Vessel Occlusion, Binary Restenosis, Clinically Driven Target Lesion Revascularization and Major Amputation	24 months
Secondary	Secondary efficacy endpoints 5	Proportion of subjects with restenosis. Restenosis is defined by duplex ultrasonographyderived peak systolic velocity ratio of >2.0 and <4.0	6, 12 and 24 months
Secondary	Secondary efficacy endpoints 6	Amputation-free survival	6, 12, 24, 36, 48 and 60 months
Secondary	Secondary efficacy endpoints 7	Proportion of subjects with clinical success defined as Improvement of =1 category in Rutherford classification compared to the pre-procedure Rutherford classification)	6,12, 24, 36, 48 and 60 months
Secondary	Secondary efficacy endpoints 8	Proportion of subjects with technical success	From day 0 to day 1
Secondary	Secondary efficacy endpoints 9	Wound assessment. Follow-up will cease once wound completely heals as adjudicated by the core lab.	2,4,6,8,12,16, 20, 24 weeks and 48 weeks
Secondary	Secondary efficacy endpoints 10	Mean change from baseline in Toe pressure and ABI assessment	6, 12 and 24 months
Secondary	Secondary Functional endpoints 1	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.	6,12 and 24 months
Secondary	Secondary Functional endpoints 2	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).	6,12 and 24 months