SELUTION4BTK Trial

Study Overview
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Brief Summary
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This study aims to demonstrate superior efficacy and equivalent safety of the SELUTION SLR™ DEB 014 compared to plain (uncoated) balloon angioplasty in the treatment of peripheral arterial disease (PAD) in the BTK arteries in CLTI patients.

Official Title
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SELUTION SLR™ 014 BTK: A Prospective Randomized Multicenter Single Blinded Study to Assess the Safety and Effectiveness of the SELUTION SLR™ 014 Drug Eluting Balloon in the Treatment of Below-the-Knee (BTK) Atherosclerotic Disease in Patients With Chronic Limb Threatening Ischemia (CLTI)

Conditions
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Peripheral Arterial Disease, Chronic Limb-Threatening Ischemia Nos of Native Arteries of Extremities

Intervention / Treatment
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* Device: SELUTION SLR™ DEB 014
* Device: Plain (Uncoated) Balloon Angioplasty (PTA)


Participation Criteria
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Eligibility Criteria
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Clinical Inclusion Criteria: Subject age is ≥ 18 years or older depending on local regulations. Subject life expectancy is ≥ 1 year. Subject has documented chronic limb-threatening ischemia in the target limb with Rutherford classification category 4, 5 or 6 and symptoms of > 2 weeks duration. Subject is willing and able to provide written informed consent and comply with study procedures and required follow-up evaluations. Female subjects only: If female, then subjects of childbearing potential must be non-breastfeeding and have a negative pregnancy test ≤ 7 days before the procedure and be prepared to use effective contraception for 24 months after treatment. Angiographic Inclusion Criteria: Target lesion(s) must lie distal to the tibial plateau and above the tibiotalar joint line within the BTK arteries. There is no limitation on total target lesion length. Two in-line areas of stenosis are considered multiple lesions if a) there is 2 cm of normal appearing artery between them, and b) at least 1 cm of the normal appearing artery is not treated. Otherwise, the lesions should be considered a single lesion and the entire segment should be treated with the assigned devices. If multiple SELUTION™ SLR DEB are used, the total allowable drug dose per patient by summing the drug dose per individual balloons must be ≤ 7069μg. Distal tibial and pedal runoff for each target lesion treated is patent (defined as <50% stenosis of the associated distal tibial artery and pedal outflow arteries). Target vessel reference diameter(s) are ≥ 2mm and ≤ 4mm. Arterial inflow (ipsilateral common iliac, external iliac, common femoral and profunda femoris arteries, SFA and popliteal artery proximal to the tibial plateau) is free from ≥ 50% stenosis as confirmed on angiography. If ≥ 50% inflow stenosis of the common and external iliac, superficial femoral, and proximal popliteal arteries is found, it must be successfully treated during the index procedure. Completion angiography must confirm successful treatment of inflow disease (≤30% residual stenosis, no distal embolization, and no Grade C or greater dissection ) prior to pre-dilation and randomization of the BTK target lesion(s). Successful pre-dilatation (defined by ≤ 30% residual stenosis, no distal embolization, and no Grade C or greater dissection) of all target lesions with uncoated PTA catheter sized to the reference vessel diameter must be accomplished before randomization. Clinical Exclusion Criteria: Subject underwent failed POBA intervention on the target lesion(s) within 3 months of the index procedure. Subject underwent surgical or endovascular procedure within 14 days prior to index procedure, or is planned for surgical or endovascular procedure within 30 days following index procedure, with the exception of: Diagnostic angiography prior to index procedure Treatment of contralateral iliac disease and/or treatment of inflow disease of the index limb that is completed prior to randomization Planned amputation of digit(s) of the index limb at the phalangeal level Debridement of a foot wound Subject has infrainguinal disease in the contralateral leg that requires treatment at the index procedure, or treatment planned to occur within 14 days prior to the index procedure or within 30 days after the index procedure. Subject is planned to undergo major amputation of either leg. Subject has undergone any prior major amputation of the ipsilateral extremity. Subject is unable to tolerate dual antiplatelet therapy. Subject has undergone non-coronary artery treatment with any limus based drug-coated or drug-eluting balloon/stent/other device within one year prior to index procedure. Subject has undergone prior DCB, DES or BMS treatment of current target lesion(s). Subject has known hypersensitivity or allergy to Sirolimus or other pharmacologic agents (such as contrast agent, heparin, bivalirudin) required for the procedure, and this hypersensitivity/allergy cannot be adequately pre-treated. Subject has experienced stroke or MI within 3 months of index procedure. Subject had onset of index limb symptoms less than 14 days prior to index procedure (acute limb ischemia). Subject has undergone prior bypass of arteries of the index limb (except for iliac artery bypass). Subject has non-atherosclerotic disease of the index limb (including aneurysmal disease, vasculitis, Buerger's disease) Subject has target lesion(s) that require (pre-)treatment with alternative therapies such as thrombolysis, thrombus aspiration, cutting/scoring/contoured balloon, stenting, laser, cryoplasty, brachytherapy, intravascular lithotripsy, or re-entry device. Subject has target lesion(s) that require treatment via pedal site. Subject has target lesion(s) that require access via upper extremity arteries. Subject has extensive tissue loss salvageable only with complex foot reconstruction or non-traditional trans metatarsal amputations. This includes subjects with: Osteomyelitis involving, more proximal to, the metatarsal head(s) Any heel wound or 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 Venous or mixed wounds. Subject has hypercoagulable state or disorder, or coagulopathy, including platelet count less than 100,000 per microliter. Subject has systemic infection (WBC > 12,000 and febrile). [Note: Enrollment permitted after successful treatment of infection with resolution of leukocytosis and/or febrile state]. Subject has known immune compromise (e.g., HIV, SLE) or is receiving treatment with immune suppressive medications. Subject is receiving (or is scheduled to receive) cancer treatment with surgery or chemotherapy or radiation therapy, or has metastatic malignancy. Subject has acute renal insufficiency confirmed through 50% increase of serum creatinine within 48 hours before procedure and/or decrease in urine output. Subject with renal transplantation. Subject has supplemental O2-dependent COPD. Subject has NYHA class IV congestive heart failure. Subject has unstable angina. Subject is bedridden. Subject has a body mass index (BMI) < 18. Subject is currently participating in another investigational drug or device study that has not completed primary endpoint follow-up. Subject has other anatomic, medical, social, or psychological conditions that in the investigator's opinion could limit the patient's ability to participate in the clinical study and/or comply with the follow-up requirements. Subject is unable to provide valid written consent for study participation (study participants cannot have informed consent provided by legal guardian or family member). Angiographic Exclusion Criteria: Presence of a previously placed stent in the target vessel(s), with the exception of: Target lesion located ≥30mm from stent, AND ≤ 30% in-stent-restenosis Failure to successfully cross the target lesion. Residual stenosis > 30%, distal embolization, and Grade C or greater dissection after pre-dilatation of target lesion . Intra-arterial thrombus, thromboembolism or atheroembolism in the index limb noted on initial diagnostic angiography or following treatment of inflow disease. Requires treatment of the tibial arteries distal to the tibiotalar joint line, or treatment of the pedal arteries.

Ages Eligible for Study
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Minimum Age: 18 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: SELUTION SLR™ DEB 014<br> | Device: SELUTION SLR™ DEB 014<br>* a non-surgical procedure that uses a catheter to inflate a drug-eluting balloon to open up peripheral below-the-knee arteries that have been narrowed by chronic limb-threatening ischemia<br>|
| Active Comparator: Plain (Uncoated) Balloon Angioplasty (PTA)<br> | Device: Plain (Uncoated) Balloon Angioplasty (PTA)<br>* a non-surgical procedure that uses a catheter to inflate a commercially available, non-drug-eluting balloon to open up peripheral below-the-knee arteries that have been narrowed by chronic limb-threatening ischemia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from target lesion occlusion, above-ankle amputation, or clinically driven target lesion re-intervention (CD-TLR) |  | 6 months | 
| Freedom from Major Adverse Limb Event (MALE) and all-cause perioperative death (POD) |  | 30 days |