SELUTION 4 De Novo Small Vessel IDE Trial

Study Overview
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Brief Summary
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Prospective, randomized controlled, single-blind, multicenter, clinical trial to demonstrate the safety and efficacy of the SELUTION SLR 014 PTCA DEB for treatment of de novo lesions in small coronary vessels, defined as reference vessel diameter (RVD) of 2.00 mm to 2.75 mm, in support of a pre-market approval (PMA) application to the United States (US) FDA. The Study will enroll up to 910 randomized subjects, up to 30 subjects in a parallel angiographic substudy, and up to 20 subjects in a parallel pharmacokinetic (pK) substudy, at up to 80 sites in the US, Canada, Brazil, Japan and Europe. A minimum of 50% of the subjects will be enrolled in the US.

Detailed Description
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Prospective, randomized controlled, single-blind, multicenter, clinical trial The study will enroll up to 910 randomized subjects, up to 30 subjects in a parallel angiographic substudy, and up to 20 subjects in a parallel pharmacokinetic (pK) substudy, at up to 80 sites in the US, Canada, Brazil, Japan and Europe. A minimum of 50% of the subjects will be enrolled in the US. Subjects who present with chronic coronary syndrome (CCS), unstable angina or stabilized non-ST elevation myocardial infarction (NSTEMI) with an indication for percutaneous coronary intervention (PCI) with planned intervention for de novo lesions in small coronary vessels (RVD 2.00 mm to 2.75 mm) and meeting all eligibility criteria will be randomized 1:1 to treatment of the identified target lesion with either the SELUTION SLR 014 PTCA DEB or contemporary DES. Randomized Cohort: Intervention (DEB Strategy): Subjects randomized to the SELUTION SLR 014 PTCA DEB arm will receive lesion preparation according to the 3rd drug coated balloon (DCB) consensus (optimal balloon angioplasty with adjunct treatment using high-pressure balloon, shockwave, rotational atherectomy or cutting or scoring balloon at the discretion of the operator as needed to reduce diameter stenosis to < 30%). Subjects with lesions that are then best treated by provisional stenting (flow-limiting dissection, residual stenosis > 30%) will receive a DES instead of the SELUTION DEB but remain in the SELUTION DEB group (intention to treat analysis). The DEB should not be used after DES implant. Control (DES): Subjects randomized to the DES arm will receive treatment using any FDA approved limus-based DES, as per standard institutional practice. Angiographic Substudy: The angiographic substudy is a parallel registry consisting of up to 30 additional consecutive subjects meeting all eligibility criteria treated with the SELUTION DEB recruited at select study sites. These subjects will undergo angiography at 12 months post-procedure. Clinical follow-up will not extend beyond 12 months in this cohort. Pharmacokinetic (pK) Substudy: The pKsubstudy is a parallel registry consisting of up to 20 additional consecutive subjects meeting all eligibility criteria treated with the SELUTION DEB recruited at select study sites. This study will be conducted under an approved substudy protocol and will include blood draws at regular intervals to characterize the pK plasma profile of sirolimus. Primary Endpoint: Target lesion failure (TLF), defined as the composite of cardiac death, target-vessel myocardial infarction (MI) or clinically-driven target lesion revascularization (TLR) at 12 months. MI includes spontaneous (Type 1) MI using the 4th Universal Definition of Myocardial Infarction (UDMI) and peri-procedural MI using the Society for Cardiac Angiography and Intervention (SCAI) definition.

Official Title
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A Prospective Randomized Single-Blind Multicenter Study to Assess the Safety and Effectiveness of the SELUTION SLR™ 014 PTCA Drug Eluting Balloon in the Treatment of Subjects With De Novo Coronary Lesions in Small Vessels

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: PCI with SELUTION SLR DCB
* Device: PCI with FDA approved -limus DES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical Inclusion Criteria Subjects must meet all of the following clinical criteria to participate in the trial: Subject is ≥ 18 years (or the minimum legal age as required by local regulations). Female subjects of childbearing potential must have a negative pregnancy test ≤ 7 days before the procedure or are using a contraceptive device or drug. Subject presents with chronic coronary syndromes [CCS] (manifest as documented angina or positive functional testing), unstable angina or stabilized non-ST elevation myocardial infarction (NSTEMI) (biomarkers stabilized or down trending) with an indication for PCI and planned intervention. Subject can tolerate dual antiplatelet therapy with aspirin, plus either Clopidogrel, Prasugrel, or Ticagrelor. (Note: For subjects requiring oral anticoagulation, aspirin may be omitted based on investigator discretion). Subject has life expectancy > 1 year in the opinion of the investigator. Subject is willing and able to provide informed consent and comply with study procedures and required follow-up evaluations. Imaging Inclusion Criteria Subject's target lesion(s) must meet all of the following angiographic criteria for the subject to participate in the trial: Up to 2 target lesions that meet criteria can be treated in a single vessel, however no non-target lesions can be treated within the target vessel in the index procedure. Non-target lesions within the target vessel can be staged for treatment > 30 days from the index procedure. Up to two (2) non-target lesions in a single non-target vessel may be treated, but successful PCI of the non-target lesions must be completed before treatment of the target lesion. Target lesion is < 36 mm in length. Target lesion has diameter stenosis > 50% and ≤ 99% with distal flow at least thrombolysis in myocardial infarction (TIMI) 2. Target vessel has RVD of ≥ 2.00 mm and ≤ 2.75 mm [by visual assessment]. Target lesion is within a native coronary artery or major branch. A target lesion within or near a bifurcation is allowed only if a single vessel (either main vessel or side branch) is to be treated. The identified target lesion has high probability for successful treatment with approved pre-treatment techniques and DEB alone. Exclusion Criteria: Clinical Exclusion Criteria Subjects who meet any of the following clinical criteria will be excluded from the trial: Subject with known hypersensitivity or allergy to Sirolimus or other pharmacologic agents required for the procedure. Subject presents with NSTEMI and rising biomarkers, or ongoing chest pain or is hemodynamically instable. Subject with history of ST-elevation myocardial infarction (STEMI) within 30 days of the index procedure. Subject with planned major surgery within 30 days following the index procedure. Subject with planned treatment of lesion involving aorto-ostial location. Subject with planned PCI of a non-target vessel within 30 days following the index procedure. Subject with history of New York Heart Association (NYHA) class III or IV heart failure. Subject with history of active peptic ulcer or gastrointestinal bleeding within 6 months of the index procedure or other inability to comply with the recommended duration of dual antiplatelet therapy (DAPT). Subject is pregnant, breast-feeding or a woman of childbearing potential or who plans pregnancy up to 1 year following index procedure. Subjects with documented left ventricular ejection fraction (LVEF) < 30%. Subject is considered not able to tolerate at least 30 seconds of coronary occlusion for each target lesion. Subjects is currently participating in another investigational drug or device study that has not completed primary endpoint follow-up. Subject with definite clinically active COVID-19 infection. Angiographic Exclusion Criteria Subject whose target lesion(s) meet any of the following angiographic criteria will be excluded from the trial: Target lesion is totally occluded or has evidence of thrombus. Target lesion is located in the left main or any arterial or venous graft. Target lesion is in a side branch that is jailed by a main vessel stent.

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: Randomized Control Trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SELUTION SLR 014 PTCA DEB<br>SELUTION Sustained Limus Release (SLR) 014 Percutaneous Transluminal Coronary Angioplasty (PTCA) Drug Eluting Balloon (DEB) The SELUTION SLR 014 PTCA DEB is a minimally invasive, single use and sterile Sirolimus coated PTCA balloon catheter. The SELUTION SLR 014 PTCA DEB is available with balloon diameters from 2.0 to 3.0 mm and lengths of 15 to 40 mm for the purpose of the De Novo IDE trial | Device: PCI with SELUTION SLR DCB<br>* After target lesion pre-dilatation and preparation , a SELUTION SLR 014 PTCA DEB study device should be selected with nominal diameter equal to the RVD of the target lesion (1:1 ratio) and length that allows approximately 2.00 mm longer than the proximal and distal edges of the target lesion (defined as the proximal and distal extent of predilation). If IVUS is performed to assess RVD, and DEB upsizing is deemed clinically necessary for optimal results, a maximum nominal DEB diameter of 3.0 mm is permitted. The SELUTION SLR 014 PTCA DEB should then be delivered, positioned in and deployed per instructions per use. The balloon should be inflated for 60 seconds provided that the patient can tolerate this duration. The minimum inflation time is 30 seconds. Where initial balloon inflation time is below the minimum 30 seconds an additional (new/unused) SELUTION SLR 014 PTCA DEB should be used following the same inflation guidelines (target 60 seconds, minimum 30 seconds).<br>|
| Active Comparator: Control Treatment<br>any FDA approved limus-based Drug Eluting Stent, as per standard institutional practice | Device: PCI with FDA approved -limus DES<br>* For subjects randomized to the control group (DES), the treating physician will choose an FDA cleared DES and follow lesion preparation and stent deployment according to the Instructions per use (IFU) and institutional practices. The DES should be sized per IFU with respect to the vessel RVD. The use of IVUS or OCT is encouraged to guide optimal stent placement and assess final results. After DES deployment, additional balloon inflations should be performed as needed to obtain < 30% residual diameter stenosis and resolve proximal or distal edge dissections greater than or equal to NHLBI grade B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target lesion failure (TLF) | Target lesion failure (TLF) is defined as the composite of cardiac death, target-vessel myocardial infarction (MI) or clinically-driven target lesion revascularization (TLR) at 12 months. MI includes spontaneous (Type 1) MI using the 4th Universal Definition of Myocardial Infarction (UDMI) and peri-procedural MI using the Society for Cardiac Angiography and Intervention (SCAI) definition. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient oriented Composite Endpoint (POCE) | Composite safety endpoint, defined as the patient-oriented composite of any death, any MI (spontaneous or peri-procedural), or any repeat revascularization. | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Lesion Success | Lesion success, defined as attainment of < 30% residual stenosis of target lesion using any percutaneous method | Up to 7 days | 
| Procedure Success | Procedure success, defined as attainment of < 30% residual stenosis of the target lesion using the assigned study device only without the occurrence of in-hospital major adverse cardiac events (MACE), composite of all-cause death, MI or any clinically-driven TLR. | Up to 7 days | 
| All-Cause Mortality |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Cardiovascular Mortality |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| MI (spontaneous MI using the 4th UDMI, peri-procedural MI using SCAI and Academic Research Consortium [ARC]-2 definitions) |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Clinically-driven TLR |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| all TLR |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Clinically-driven Target Vessel Revascularization (TVR) |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| all TVR |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Non-target lesion revascularization |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Target Vessel Failure (TVF) | Target vessel failure (TVF), defined as a composite of: cardiac death, target vessel MI (spontaneous or peri-procedural) and any clinically-driven TVR | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Stent or target lesion segment thrombosis (definite or probable) according to the ARC criteria for acute, subacute, late, very late and cumulative stent thrombosis |  | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Bleeding Academic Research Consortium (BARC) class 2-5 |  | 12 months | 
| Net adverse clinical events (NACE) | Net adverse clinical events, defined as death, MI (spontaneous or peri-procedural), TVR, stent/target lesion segment thrombosis or bleeding (BARC types 2-5, assessed to 12 months) | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | 
| Target lesion Failure |  | Up to 7 days and at 1 month, 6 months, 2 years, 3 years, 4 years, and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SELUTIONSLR, CAD, DCB, DEB, NSTEMI, Stable Angina, Chronic Coronary Syndrome, CCS, Drug Coated Balloons, Drug Eluting Balloons, Small Vessels, Sirolimus