This is a Pivotal, Prospective, randomized, two arm, placebo controlled, single-blind, multicenter trial that will be conducted at approximately 80 sites; approx. 50 sites with at least 50% of subjects will be recruited from USA and approx. 30 sites OUS - Europe, Australia and Asia. 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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
368
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.
For participants randomized to a Placebo balloon angioplasty group, a Placebo balloon angioplasty in addition to standard balloon angioplasty will be performed.
Honor Health Research & Innovation Institute
Scottsdale, Arizona, United States
RECRUITINGCedars-Sinai Medical Center
Los Angeles, California, United States
RECRUITINGUniversity of California Los Angeles
Los Angeles, California, United States
NOT_YET_RECRUITINGClearwater Cardiovascular Consultants
Clearwater, Florida, United States
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.
Time frame: 12 months
Composite safety endpoint
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.
Time frame: 6-months for n.1 and n.2; 30 days for n.3
Secondary Safety endpoint 1
Proportion of device and procedure related death
Time frame: 1, 6, 12, 24, 36, 48 and 60 months
Secondary Safety endpoint 2
Proportion of subjects with death by any cause
Time frame: 1, 6, 12, 24, 36, 48 and 60 months
Secondary Safety endpoint 3
Proportion of subjects with major target limb amputation
Time frame: 1, 6, 12, 24, 36, 48 and 60 months
Secondary Safety endpoint 4
Proportion of subjects with target vessel thrombosis
Time frame: From day 0 to day 14
Secondary Safety endpoint 5
Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure
Time frame: From day 0 to 60 months
Secondary efficacy endpoints 1
Proportion of subjects with acute procedural success
Time frame: From day 0 to 60 months
Secondary efficacy endpoints 2
Proportion of subjects who are free from clinically driven Target Lesion Revascularization (CD-TLR)
Time frame: 6, 12, 24, and 36 months
Secondary efficacy endpoints 3
Proportion of subjects who are free from Target Vessel Revascularization (TVR)
Time frame: 6,12,24 and 36 months
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
Time frame: 24 months
Secondary efficacy endpoints 5
Proportion of subjects with restenosis. Restenosis is defined by duplex ultrasonography-derived peak systolic velocity ratio of \>2.0 and \<4.0
Time frame: 6, 12 and 24 months
Secondary efficacy endpoints 6
Amputation-free survival
Time frame: 6, 12, 24, 36, 48 and 60 months
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
Time frame: 6,12, 24, 36, 48 and 60 months
Secondary efficacy endpoints 8
Proportion of subjects with technical success
Time frame: From day 0 to day 1
Secondary efficacy endpoints 9
Wound assessment. Follow-up will cease once wound completely heals as adjudicated by the core lab.
Time frame: 1, 3, 6, and 12 months
Secondary efficacy endpoints 10
Mean change from baseline in Toe pressure and ABI assessment
Time frame: 6, 12 and 24 months
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.
Time frame: 6,12, 24, and 36 months
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).
Time frame: 6,12, 24, and 36 months
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Baptist Hospital of Miami
Miami, Florida, United States
RECRUITINGUniversity of South Florida
Tampa, Florida, United States
RECRUITINGVascular Institute of the Midwest
Davenport, Iowa, United States
RECRUITINGUnity Point Health Des Moines
Des Moines, Iowa, United States
RECRUITINGAtria Vascular and Vein
Farmington Hills, Michigan, United States
NOT_YET_RECRUITINGDeborah Heart and Lung Center
Browns Mills, New Jersey, United States
RECRUITING...and 19 more locations