SELUTION SLR™ 014 In-stent Restenosis

Study Overview
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Brief Summary
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Prospective, multi-center, randomized, single blind, controlled, noninferiority clinical trial. Subjects with previous bare-metal or drug-eluting coronary stent will be randomized 1:1 to treatment with either the SELUTION SLR™ DEB or SOC to include contemporary DES (zotarolimus-eluting stents and everolimus-eluting stents only) or non-DEB BA. A maximum of 418 randomized subjects will be included. Subjects will be followed for 5 years post-intervention. Primary endpoint will be target lesion failure (TLF) determined at 12-month clinical follow-up.

Detailed Description
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Prospective, multi-center, randomized, single blind, controlled, noninferiority clinical trial. Subjects with previous bare-metal or drug-eluting coronary stent and qualifying evidence for ISR will be screened per the protocol inclusion and exclusion criteria to achieve a maximum of 418 randomized subjects (includes 5% allowance for loss to follow-up). Eligible subjects will be randomized 1:1 to treatment with either the SELUTION SLR™ DEB or SOC to include contemporary DES (zotarolimus-eluting stents and everolimus-eluting stents only) or non-DEB BA. A maximum of 20% of patients randomized to SOC will be treated with BA. Randomization will be stratified by DES or bare-metal stent (BMS) ISR and whether there has been previous repeat stenting of target lesion. Subjects with > 2 previous repeat stent procedures involving the target lesion will be excluded. The study will test for noninferiority of DEB versus SOC and additionally noninferiority of DEB vs DES. Primary endpoint will be target lesion failure (TLF) determined at 12-month clinical follow-up. After initial randomized treatment subjects in the SOC group may receive DEB (including SELUTION SLR™) treatment for recurrent clinical restenosis requiring a repeat target lesion revascularization (TLR) (i.e. after the study primary endpoint has been failed). A subset of subjects (120 subjects including the first 60 randomized in the United States (US) and first 60 randomized in Europe who receive successful study treatment) will undergo planned angiographic follow-up at 12-13 months after completion of primary endpoint clinical follow-up/assessment. At 12-13 months, and after clinical primary endpoint has been assessed, a subset of the angiographic follow-up cohort ( 60) will also undergo planned optical coherence tomography (OCT) follow-up, 30 United States (US) and 30 Europe.

Official Title
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SELUTION SLR™ 014 ISR: A Prospective Randomized Single Blind Multicenter Study to Assess the Safety and Effectiveness of the SELUTION SLR™ 014 Drug Eluting Balloon in the Treatment of Subjects With In-stent Restenosis

Conditions
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Coronary Restenosis

Intervention / Treatment
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* Device: SELUTION SLR™ DEB
* Device: Control


Participation Criteria
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Eligibility Criteria
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Clinical Inclusion Criteria: Subject age is ≥ 18 years or minimum legal age as required by local regulations. Female subjects of childbearing potential have a negative pregnancy test ≤ 7 days before the procedure. Documented stable or unstable angina including non-ST-elevation MI or functional testing demonstrating ischemia. Subject is eligible for dual antiplatelet therapy (DAPT) treatment with aspirin plus either, Clopidogrel, Prasugrel, or Ticagrelor. Life expectancy >1 year in opinion of investigator. Subject is willing and able to provide informed consent and comply with study procedures and required follow-up evaluations. Angiographic Inclusion Criteria Target lesion is within a previously placed BMS or DES and does not extend > 5.00 mm beyond proximal or distal edge. Target lesion is < 36 mm in length. Target lesion has diameter stenosis of > 50% and < 100% with distal flow at least Thrombolysis in Myocardial Infarction (TIMI) 2. RVD is ≥ 2.00 mm and ≤ 4.50 mm. Target lesion is within a native coronary artery or major branch. Up to two (2) non-target lesions in non-target vessels may be treated, but successful percutaneous coronary Intervention (PCI) must be completed before treatment of target lesion. Clinical Exclusion Criteria: Known hypersensitivity or allergy to Sirolimus or other pharmacologic agents required for the procedure. ST-elevation myocardial infarction (STEMI) within 30 days. Planned treatment of additional lesions in target vessel or > two (2) non-target lesions within non-target vessels during index procedure. Planned treatment of lesion involving bifurcation or aorto-ostial location. Target lesion has undergone > two (2) prior stent implant procedures (including the initial index procedure, i.e., > two (2) layers of stent are present at any segment of target lesion). Any previous brachytherapy of the target vessel. Previous PCI of the target vessel within 30 days. Planned PCI of a non-target vessel within 30 days of randomization. Planned use of atherectomy (rotational, orbital, or laser) device. Use of cutting or scoring balloon is allowed. History of active peptic ulcer or gastrointestinal bleeding within prior 6 months or other inability to comply with recommended duration of DAPT. Subject is pregnant, breast-feeding, or a woman of childbearing potential who is not using appropriate contraceptives to avoid becoming pregnant. Documented left ventricular ejection fraction (LVEF) < 25%. Currently participating in another investigational drug or device study that has not completed primary endpoint follow-up. Angiographic Exclusion Criteria Target lesion is totally occluded or has evidence of thrombus. Target lesion is severely calcified, defined as visual calcification involving both walls of the target segment as seen on a non-contrast still image. Stent diameter <80% of RVD after high pressure stent expansion. >30% residual stenosis after pre-dilation.

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
Interventional Model Description: Randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SELUTION SLR™ DEB<br> | Device: SELUTION SLR™ DEB<br>* The SELUTION Sustained Limus Release (SLR)™ drug-eluting balloon (DEB) catheter is a combination product consisting of a standard percutaneous transluminal angioplasty (PTA) balloon catheter coated with a drug (Sirolimus). The drug coating is formulated with Sirolimus microspheres suspended in a phospholipid blend. The balloon catheter component of the SELUTION SLR™ DEB is a conventional single use, sterile, rapid exchange catheter to dilate vascular lesions. The semi-compliant balloon is inflated for 60 seconds (minimum of 30 seconds) to transfer the Sirolimus loaded microspheres to the target vessel wall. The balloon is then deflated and removed from the body.<br>|
| Active Comparator: Control Treatment<br>For subjects randomized to the control group (SOC) the treating physician may chose to implant a commercially available DES or alternatively may use POBA only to treat the patient. The decision should be based on the treating physicians' assessment of the best treatment option for the individual patient. However, it is expected that patients with one prior stent will receive DES and patients with two prior stents will receive POBA. Treating physicians may deviate from this if it is determined to be in the best interest of the patient, but the justification for the treatment decision must be recorded in eCRF. Choice of DES is at the treating physician's discretion, but is limited to ZES and EES devices. | Device: Control<br>* The treating physician may chose to implant a commercially available DES or alternatively may use POBA only to treat the patient. Choice of DES is at the treating physician's discretion, but is limited to ZES and EES devices<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Lesion Failure | The primary endpoint for effectiveness is target lesion failure (TLF) rate at 12 months post-index procedure. TLF is defined as a composite of: all cardiac death, target vessel myocardial infarction (SCAI definition), and clinically driven TLR. | 12 months post-index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-segment minimal luminal diameter (MLD) | The powered secondary endpoint will be in-segment minimal luminal diameter (MLD) at 12 months (after documented completion of 12 months of clinical follow-up) in the angiographic follow-up subset. | at 12 months | 
| Device success | Attainment of < 30% residual stenosis of the target lesion using the assigned study treatment only. | at 12 months | 
| Lesion Success | Attainment of < 30% residual stenosis of target lesion using any percutaneous method. | at 12 months | 
| Procedure Success | Attainment of < 30% residual stenosis of the target lesion using the assigned study device only without occurrence of in-hospital MACE. | at 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In-stent restenosis, Drug Eluting Balloon, Coronary