ADVANCEd NanoTherapies Dual Active Pharmacological Ingredient (Dual-API) Drug-Coated Balloon to Treat De-Novo Lesions in Patients With Symptomatic Stable Coronary Artery Disease

Study Overview
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Brief Summary
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This prospective, single-arm, multi-center, safety and feasibility first-in-human study will evaluate the safety and feasibility of the SirPlux™ Duo Dual-API Coated PTCA Balloon Catheter to treat de-novo lesions between ≥2.25 and ≤4.0 mm in patients with stable symptomatic coronary artery disease.

Detailed Description
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The SirPlux Duo™ Dual API-Coated PTCA Balloon Catheter is an investigational medical device to be used to treat de-novo lesions in patients with symptomatic coronary artery disease. In this study, SirPlux Duo™ will be used in subjects undergoing a planned percutaneous coronary intervention. Population to treat will include those with de-novo coronary lesions in vessels with a reference vessel diameter (RVD) of ≥2.25 and ≤4.0 mm and a total lesion length of <35mm with documented symptomatic stable coronary artery disease. The study is a prospective, single-arm, multi-center, safety and feasibility first-in-human study designed to generate descriptive data about the use of SirPlux Duo™. The study primary performance endpoint is device success, technical success and procedural success. The safety primary endpoint (angiographic endpoint) is In-segment Late Lumen Loss (LLL) at 6 months. Other safety secondary clinical and angiographic endpoints (detailed below) will me measured during procedure up to 24 hours after discharge, at 30 days, 6 months, 12 months and 24 months after procedure.

Official Title
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A Prospective, Single-arm, Multi-center, Feasibility First-in-human Study to Evaluate Safety and Performance of the SirPlux Duo™ Dual-API Coated PTCA Balloon Catheter to Treat De-novo Lesions in Patients With Symptomatic Stable Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: SirPlux™ Duo Dual-API Coated PTCA Balloon Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is ≥18 years and <90 years old. Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed. Life expectancy > 1 year. The subject is intended to undergo an angiographic procedure and coronary percutaneous intervention. The subject is an acceptable candidate for treatment in the Investigator's opinion and/or per hospital guidelines. The subject is intended to undergo treatment with a coronary drug-coated balloon. Women of child-bearing potential must agree to use a reliable method of contraception from the time of screening through 12 months after the index procedure. Men with a female partner of childbearing potential must agree to use condoms plus an additional reliable contraceptive method within 12 months after the index procedure. The subject is able and willing to comply with all assessments in the study, including dual antiplatelet therapy (DAPT), ASA indefinitely, and P2Y12 inhibitor for a minimum of 6 months. The subject shall be under optimal medical therapy for ASCVD, which includes at a minimum high-intensity statin therapy (atorvastatin 40-80 mg/d or rosuvastatin 20-40 mg/d). If statin intolerant, the patient should be treated with a PCSK9 inhibitor, ezetimibe or bempedoic acid. Subject has chronic stable angina or has had an acute coronary syndrome and the cardiac biomarkers have returned to normal Target lesion is located within a de-novo coronary artery located in a native coronary artery with a reference vessel diameter between ≥2.25 mm to ≤4.0mm by visual estimate, with a lesion length of equal greater 15mm to < 35mm. Subject has multiple lesions that meet inclusion and exclusion criteria individually that could be treated with a study device. To be treated with a study device, lesions must be defined as target lesions. A maximum of three (3) lesions could be treated during the index procedure (maximum of 2 target vessels). One (1) non-target lesion can be staged if needed. Target lesions (up tp 2) cannot be staged. One investigational device is to be used per target lesion. Successful pre-dilation with semi and/or non-compliant balloon of the target lesion(s) is defined as no major flow-limiting dissections (Grade C or higher) and ≤30% residual stenosis of the target lesion by a visual estimate on angiography. Adjunctive therapy pre-dilation therapies such as scoring balloon, cutting balloon, and IVL are allowed. Rotablator or similar rotational atherectomy devices are restricted per protocol. Exclusion Criteria: General Exclusion Criteria: Subject has other serious medical illnesses (e.g., cancer, congestive heart failure) that may reduce life expectancy to less than 12 months. Subject has current problems with substance abuse. Subject has a planned procedure that may cause non-compliance with the protocol or confound data interpretation. Subject participates in another investigational drug or device clinical study that has not reached its primary endpoint. Subject intends to participate in another investigational drug or device clinical study within 12 months after the index procedure. Significant target vessel tortuosity or other parameters that could prohibit access to the target lesion. Type A lesions, Chronic total occlusion (CTO) of the target lesion(s) or Thrombolysis In Myocardial Infarction (TIMI) flow < 2. Cardiogenic shock. Subject requires treatment of a coronary lesion(s) involving a bifurcation. Target lesion(s) within native or synthetic vessel grafts. CTO of inflow vessel. Subject has had any major (e.g., cardiac, peripheral, abdominal) surgical procedure or intervention unrelated to this study within 30 days before the index procedure or has a planned major surgical procedure or intervention within 30 days of the index procedure. Subject requires treatment of a coronary lesion distal to the target lesion(s) at the time of the enrollment/index procedure. The subject has a known coagulopathy or has a bleeding diathesis, thrombocytopenia (with platelet counts less than 100,000/microliter) or platelets > 400,000/microliter, or international normalized ratio >1.5. Patients on chronic oral anticoagulation medications will be excluded of the study Known renal insufficiency (e.g., serum creatinine >2.5mg/dL, or creatinine clearance (CrCl) ≤30 mL/min). Subject on dialysis, or acute kidney failure (as per physician judgment). Subject in whom antiplatelet, anticoagulant or thrombolytic therapy is contraindicated or hypersensitive. Subject has a known allergy to contrast agents or medications used to perform a coronary intervention that cannot be adequately pre-treated, including, but not limited to, sirolimus, paclitaxel, aspirin, heparin, clopidogrel bisulfate, ticlopidine, prasugrel, ticagrelor. Subject has a known allergy to urethane, nylon, or silicone. Myocardial infarction within 60 days before enrollment. History of stroke/TIA within 60 days before enrollment. LVEF <30%. Subject is confined to bed. Subject has a life expectancy less than 12 months. History of thrombolytic therapy within two weeks of enrollment. Patient is a recipient of a heart transplant. Patient is unwilling/not able to return for angiographic catheterization at 6-month follow-up. Women who are pregnant, breast-feeding or intend to become pregnant. Subject is planning to participate in other clinical studies before completing this study. Subject has other medical, social, or psychological problems and is unwilling or unable to comply with procedures specified in the protocol, or may have difficulty returning for follow-up visits as specified by the protocol. Cardiogenic shock (SBP <80mmHg requiring inotropes, IABP, or fluid support). Known allergies to sirolimus, paclitaxel or other components of the used medical devices. Subject with renal insufficiency (creatinine ≥2.0mg/dl) or failure (dialysis-dependent). Subject has suspected or proven COVID-19 positive result at present or within the past 4 weeks of informed consent form. Angiographic Exclusion Criteria: Subject has a planned intervention in the left-main plus two separate major epicardial territories (left-main plus 2 vessel diseases). Target vessel size <2.0 mm or >4.0 mm Target lesion in the left main stem and proximal LAD. The target vessel contains visible thrombus. Aorto-ostial target lesion (within 3 mm of the aorta junction); including all left main disease. Moderate-severe tortuous, calcified, or angulated coronary anatomy of the target vessel that, in the opinion of the Investigator, would result in suboptimal imaging or excessive risk of complication from placement of an IVUS catheter following Clinical Decision. The lesion is located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft. Target lesions are located within a bifurcation of the planned treatment of side-branch vessel. Target lesion is located within a previous implanted stent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, multi-center, single-arm, feasibility study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SirPlux™ Duo Dual-API Coated PTCA Balloon Catheter<br>Subjects who meet the inclusion criteria and agree to participate in the study will be enrolled and undergo a planned percutaneous coronary intervention with SirPlux™. | Device: SirPlux™ Duo Dual-API Coated PTCA Balloon Catheter<br>* SirPlux™ Duo Dual-API Coated PTCA Balloon Catheter is a Drug-Coated Balloon to treat de novo lesions in patients with symptomatic stable coronary artery disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance Endpoint 1 | - Device Success: Defined as successful delivery, balloon inflation, deflation, and retrieval of the intact study device without burst below rated burst pressure | (Peri-procedural) | 
| Performance Endpoint 2 | - Technical Success: Defined as successful lesion crossing, completion of POBA and immediate achievement of <30% residual stenosis (by QCA) of the target lesion upon completion of angiography post investigational device inflation | (Peri-procedural) | 
| Performance Endpoint 3 | - Procedural Success: Defined as device success or technical success and absence of procedural complications following SirPlux Duo™ Dual-API Coated PTCA Balloon Catheter inflation (ie absence of vessel dissection or loss of TIMI 3 flow) | (Peri-procedural) | 
| Angiographic Endpoint (by QCA): | In-segment Late Lumen Loss (LLL) | at 6 months after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint | All-cause death Target Vessel Myocardial Infarction (TVMI). Cardiac death Myocardial Infarction (MI) Emergent Coronary Artery Bypass Graft (CABG) Repeat Target Lesion Revascularization (TLR) (clinically driven) by percutaneous or surgical methods Major Adverse Cardiac Event (MACE) Target Vessel Failure (TVF) Target Lesion Failure (TLF) All revascularizations (TLR, TVR and non-TVR) | During procedure up to 24 hours, at 30 days, 6 months, 12 months and 24 months | 
| Angiographic and IVUS Endpoint | In-segment ( and in balloon) percent diameter stenosis (% diameter stenosis; DS). | at 6 months post-procedure | 
| Angiographic and IVUS Endpoint | in-segment binary angiographic restenosis (BAR) rate [defined as ≥50% DS]. | at 6 months post-procedure | 
| Angiographic and IVUS Endpoint | • In-segment (and in balloon) Minimum Luminal/Lumen Diameter (MLD) | at 6 months post-procedure | 
| Angiographic and IVUS Endpoint | • In-segment (and in balloon) Change in IVUS MLA (mm2) | at 6 months post-procedure | 
| Angiographic and IVUS Endpoint | • In-segment (and in balloon) Change in mean lumen area (mm2) | at 6 months post-procedure | 
| Angiographic and IVUS Endpoint | • In-segment (and in balloon) Change in percentage atheroma volume | at 6 months post-procedure | 
| Angiographic and IVUS Endpoint | • In-segment (and in balloon) Serial IVUS remodeling (change in vessel area/volume) | at 6 months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Coated Ballon, DCB, Coronary Artery Disease