MAGICAL BTK: Randomized Controlled Trial of MAGIcTouch - Sirolimus Coated BALloon Versus Standard Balloon Angioplasty in The Treatment of Below The Knee Arterial Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 368
- 试验地点
- 58
- 主要终点
- Composite safety endpoint
研究概览
简要总结
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:
- MagicTouch PTA sirolimus coated balloon catheter (DCB) in addition to standard balloon angioplasty or
- Placebo balloon angioplasty in addition to standard balloon angioplasty (PTA).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
This is a single-blinded clinical investigation in which subjects will be blinded.The physician performing the index procedure will not be blinded. It is recommended, where feasible, that a different physician, or qualified designee, who is blinded to the subject's treatment, conduct protocol-required follow-up visits. The Study Coordinator will be unblinded.
The technologists performing follow-up ultrasound scans, the Clinical Events Committee, the Data Safety Monitoring Board and core laboratories will be blinded. In emergency situations, the treating physician is responsible for assessing whether unblinding the treatment assignment is necessary, with the subject's safety as the first priority in making such a decision. If the treating physician decides that unblinding is warranted, the investigator will contact Concept Medical or the CRO to obtain the treatment assignment.
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 21 years or minimum age (is allowed the inclusion of subjects > 21 years OR adulthood minimum age (depending on the US state regulations)
- •Rutherford class 4 with documented WIFI score, not exceeding more than 30% of target patient population.
- •Rutherford class 5 to 6 in the target limb with documented WIFI score.
- •Intraoperative Inclusion Criteria:
- •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.
- •Target vessel has angiographically documented unimpaired (<50% stenosis) run off into a named Tibio-pedal artery (Peroneal, Anterior Tibial/ Dorsalis Pedis/ Posterior Tibial Artery)
排除标准
- •Comorbid conditions limiting life expectancy ≤ 1 year
- •Subject is currently participating in another investigational drug or device study that has not reached first primary endpoint yet
- •Subject is lactating, pregnant or planning to become pregnant during the course of the study
- •Subject with extensive tissue loss salvageable only with complex foot reconstruction or non-traditional trans metatarsal amputation. This includes subjects with:
- •Osteomyelitis including and/or proximal to the metatarsal head
- •Gangrene involving the plantar skin of the forefoot, midfoot,or heel
- •Deep ulcer or large shallow ulcer (> 3 cm) involving the plantar skin of the forefoot, midfoot, or heel
- •Full thickness heel ulcer with/without calcaneal involvement
- •Any wound with calcaneal bone involvement
- •Wounds that are deemed to be neuropathic or non-ischemic in nature
- •Wounds that would require flap coverage or complex wound management for large soft tissue defect
- •Full thickness wounds on the dorsum of the foot with exposed tendon or bone
- •Prior bypass surgery of target vessel
- •Planned amputation of the target limb (major)
- •Previously implanted stent in the target lesion
- •Vulnerable or protected adults
- •Bleeding diathesis or another disorder (i.e. gastrointestinal ulceration,etc) which would prevent the use of mandated antiplatelet agents
- •Known allergy to sirolimus
- •Subjects with severe (Stage 4) renal disease, defined eGFR <
- •Intraoperative exclusion criteria:
- •Failure to successfully cross the target lesion with a guide wire
- •Target vessel has lesions extending beyond the ankle joint
- •Failure to obtain <30% residual stenosis prior to randomization
- •Lesions requiring treatment through retrograde access . Retrograde wire crossing is allowed but treatment must be performed from the antegrade approach.
- •Use of commercially available DCBs, bare metal stents, drug eluting stents, specialty balloons or atherectomy devices at the target lesions. (Non-compliant balloons are not considered specialty balloons). For Inflow and non-target lesions all the approved devices are allowed.
结局指标
主要结局
Composite safety endpoint
时间窗: 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.
时间窗: 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.
次要结局
- Secondary efficacy endpoints 7(6,12, 24, 36, 48 and 60 months)
- Secondary efficacy endpoints 8(From day 0 to day 1)
- Secondary efficacy endpoints 10(6, 12 and 24 months)
- Secondary efficacy endpoints 5(6, 12 and 24 months)
- Secondary efficacy endpoints 6(6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 1(1, 6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 2(1, 6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 3(1, 6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 4(From day 0 to day 14)
- Secondary Safety endpoint 5(From day 0 to 60 months)
- Secondary efficacy endpoints 1(From day 0 to 60 months)
- Secondary efficacy endpoints 2(6, 12, 24, and 36 months)
- Secondary efficacy endpoints 3(6,12,24 and 36 months)
- Secondary efficacy endpoints 4(24 months)
- Secondary Safety endpoint 1(1, 6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 2(1, 6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 3(1, 6, 12, 24, 36, 48 and 60 months)
- Secondary Safety endpoint 4(From day 0 to day 14)
- Secondary Safety endpoint 5(From day 0 to 60 months)
- Secondary efficacy endpoints 2(6, 12, 24, and 36 months)
- Secondary efficacy endpoints 3(6,12,24 and 36 months)
- Secondary efficacy endpoints 1(From day 0 to 60 months)
- Secondary efficacy endpoints 4(24 months)
- Secondary efficacy endpoints 5(6, 12 and 24 months)
- Secondary efficacy endpoints 6(6, 12, 24, 36, 48 and 60 months)
- Secondary efficacy endpoints 7(6,12, 24, 36, 48 and 60 months)
- Secondary efficacy endpoints 8(From day 0 to day 1)
- Secondary efficacy endpoints 10(6, 12 and 24 months)
- Secondary efficacy endpoints 9(1, 3, 6, and 12 months)
- Secondary Functional endpoints 1(6,12, 24, and 36 months)
- Secondary Functional endpoints 2(6,12, 24, and 36 months)