IBS Titan vs. PTA in Patients With Infrapopliteal Arterial Stenosis or Occlusive Disease

Study Overview
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Brief Summary
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A prospective, multi-center, randomized trial to assess the safety and effectiveness of Sirolimus-eluting Iron Bioresorbable Peripheral Scaffold System (IBS Titan™) in treating patients with infrapopliteal arterial stenosis or occlusive disease.

Official Title
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A Prospective, Multi-Center, Randomized Trial Comparing the IBS Titan™ Sirolimus-Eluting Iron Bioresorbable Peripheral Scaffold System vs. Standard Balloon Angioplasty for Treatment of Below-the-Knee Arteries: GENIUS TRIAL

Conditions
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Critical Limb Ischemia (CLI)

Intervention / Treatment
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* Device: Sirolimus-eluting Iron Bioresorbable Peripheral Scaffold System (IBS Titan™)
* Device: Percutaneous Transluminal Angioplasty (PTA) Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must between 18 and 85 years old, without gender limit. Patients who can understand the purpose of the trial, voluntarily participate in and sign the informed consent form, and complete the 1-year follow-up. Subject has lower extremity atherosclerotic occlusive disease with symptomatic Critical Limb Ischemia (CLI). Rutherford Becker Clinical Category 3-5. The target lesion is below the popliteal artery (including bifurcation). The target lesion is located in the proximal 2/3 of native infrapopliteal vessels or tibiofibular trunk. The target lesion stenosis is ≥70% or occlusion of no more than two infrapopliteal arteries (including the anterior and/or posterior tibial and/or peroneal artery and/or tibiofibular trunk). The length of target lesion is ≤200mm, which could be covered by no more than two stents, with vessel diameter of 2.25-4.25 mm. Exclusion Criteria: Severe renal insufficiency, hepatic dysfunction (Cr>2 times of normal limit or renal dialysis, ALT or AST > 5 times of normal limit). Surgery in target vessel before treatment. Volume reduction surgery in target vessel before treatment. Thrombosis in target vessel, or acute thrombosis requiring thrombolysis and thrombectomy. Systematic coagulation disorder or hypercoagulability. Lower extremity arteries surgery or thrombolytic therapy in the ipsilateral extremity in the past 6 weeks. Stroke occurs within 3 months before surgery, or stroke occurs with severe hemiplegia aphasia sequelae more than 3 months before treatment. Acute myocardial infarction or angina pectoris within 30 days before treatment. In-stent restenosis. Guide wire cannot pass target lesion. Previously treated with drug eluting balloon within 1 year before treatment. More than two infrapopliteal arteries needed treatment. The inflow tract (including ipsilateral iliac artery, femoral artery, popliteal artery) has lumen stenosis >30% with or without intervention. The inflow tract (including ipsilateral iliac artery, femoral artery, popliteal artery) has > 150 mm stenosis or occlusion before treatment. Aneurysm of lower extremity artery. Thromboangiitis obliterans (Buerger's disease). Significant (≥ 50% stenosis) lesion in a distal outflow artery that would be perfused by the target vessel and that requires treatment at the time of the index procedure. Patients known to be allergic to aspirin, heparin, Plavix, contrast agents, Sirolimus, poly lactic acid polymer, iron, zinc and their degradation product, and those who cannot tolerate postoperative dual anti-platelet therapy. Patients who have a history of disease related to iron overload or iron disorder, such as hereditary hemochromatosis, etc. Patients who are participating in another clinical trial that has not yet completed its primary endpoint. Pregnant or those who plan pregnancy during the clinical investigation follow-up period. Angiography suggests intraoperative thromboendarterectomy, percutaneous transluminal rotational atherectomy or laser therapy are needed. Patients have life expectancy ≤ 1 year. Patients who are not suitable for participating the trial judged by investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBS Titan<br> | Device: Sirolimus-eluting Iron Bioresorbable Peripheral Scaffold System (IBS Titan™)<br>* Subjects in this arm will be treated with IBS Titan™.<br>|
| Active Comparator: Percutaneous Transluminal Angioplasty (PTA)<br> | Device: Percutaneous Transluminal Angioplasty (PTA) Device<br>* Subjects in this arm will be treated with PTA device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency Rate | Defined as freedom from total occlusion of target lesion and clinically driven target lesion revascularization (CD-TLR) of target lesion, and freedom from major amputation. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | 30 days, 180 days, 365 days | 
| Incidence of Clinically-driven Target Vessel Revascularization (CD-TLR) | CD-TLR is defined as any TLR of target lesions associated with Rutherford category exacerbation and/or increasing in the size of preexisting wounds and/or the occurrence of new wounds. | 30 days, 180 days, 365 days | 
| Incidence of major amputation | Unplanned amputation of the lower limb above the ankle on the target lesion side | 30 days, 180 days, 365 days | 
| Rate of Device Success | Device success is defined on a per device basis, as the achievement of successful delivery, deployment of stent at the intended infrapopliteal target site(s) and successful withdrawal of the delivery catheter. | Immediately after the procedure | 
| Rate of Participants with Technical Success | Defined as restoration of blood flow in the target vessel and angiogram indicates the residual stenosis <50%. | Immediately after the procedure | 
| Rate of Participants with Procedural Success | Defined as the combination of technical success, device success, and absence of procedural complications. | Immediately after the procedure | 
| Late Lumen Loss |  | 180 days | 
| Incidence of Target lesion restenosis | Defined as a reduction in the luminal diameter >50% by angiography or CTA within the treated lesion plus the 5-mm segments proximal and distal to it or, as a peak systolic velocity ratio (PSVR) >2.4 by DUS. Note 1: Doppler ultrasound will be performed at 30 days and 365 days, DSA angiography will be performed 180 days. Note 2: If the patient presented with CD-TLR in advance, i.e. the patient reached the endpoint in advance, the restenosis before reintervention was assessed. | 30 days, 180 days, 365 days | 
| Change in ankle-brachial index (ABI) compared to baseline (before treatment) |  | 30 days, 180 days, 365 days | 
| Change in Rutherford-Becker category compared to baseline (before treatment) | Categories and Clinical Description (higher scores mean a worse outcome): Category 0 = Asymptomatic, no hemodynamically significant occlusive disease, Category 1 = Mild claudication, Category 2 = Moderate claudication, Category 3 = Severe claudication, Category 4 = Ischemic rest pain, Category 5 = Minor tissue loss, non-healing ulcer, or focal gangrene with diffuse pedal ischemia, Category 6 = Major tissue loss, extending above transmetatarsal level, functional foot no longer salvageable. | 30 days, 180 days, 365 days | 
| Wound healing rate of ulcer patients |  | 30 days, 180 days, 365 days |