Biolimus A9™ (BA9™) Drug Coated Balloon (DCB) Study

Study Overview
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Brief Summary
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The study is a Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis. It is a First-in-Man Trial.

Detailed Description
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This clinical trial will serve as a first-in-human (FIH) experience for the BA9™ DCB in a population of patients with coronary artery disease who have an indication for interventional treatment of in-stent restenosis (ISR) in a bare-metal stent (BMS) or drug-eluting stent (DES). The study uses a prospective, multi-center, single blind, randomized controlled trial design to enroll 195 patients. The study will seek to prove that the BA9-DCB is non-inferior to the approved CE marked Sequent Please® Paclitaxel Coated Balloon with respect to % Diameter Stenosis and has similar safety characteristics.

Official Title
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A Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9TM Drug Coated Balloon for the Treatment of In-Stent Restenosis: First-in-Man Trial (REFORM)

Conditions
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Coronary Artery Disease, In-Stent Restenosis

Intervention / Treatment
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* Device: Biolimus A9 Drug Coated Balloon
* Device: SeQuent Please Paclitaxel Drug Coated Balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with in-stent restenosis (ISR) and clinical symptoms of ischemia and/or (i) evidence of ischemia on non-invasive testing or (ii) hemodynamically relevant lesion defined by FFR ≤ 0.80 or iFR ≤ 0.89 or > 90% stenosis. Patient presenting with a lesion that can be fully covered with one DCB length. - Patients can have up to two index lesions with ISR, which can both be treated and evaluated. Patient has provided written informed consent Age ≥ 18 years. Patient is willing and able to comply with the study procedures and follow-up. Exclusion Criteria: Patient presents with a ST-elevation myocardial infarction (STEMI) or had an acute MI within 48 hours prior to presentation (according to the universal definition of myocardial infarction). Patient with acute cardiac decompensation or acute cardiogenic shock Documented left ventricular ejection fraction (LVEF) ≤ 30% Patient with impaired renal function (glomerular filtration rate < 80 mL/min/1.73 m2). More than 2 epicardial vessels requiring revascularization Significant left main stenosis (by visual estimation) or an ISR located in the left main (LM). Patient has an ISR lesion that cannot be covered with one DCB length. Patient has an ISR in the target segment in a stent of a smaller diameter than 2.5mm. Severe calcification that might prevent a sufficient expansion of the DCB, if not pre-treated with rotablation or a shockwave application device. Known hypersensitivity or contraindication to biolimus, paclitaxcel, aspirin, thienopyridines, or iodinated contrast that cannot be pre-treated. Pregnant and/or breast-feeding females or females who intend to become pregnant during the time of the study. Subject currently enrolled in other investigational device or drug trial in which the primary endpoint has not yet been reached. Anticipated difficulties to complete the angiographic follow-up study. Patient with a life expectancy of less than 12 months. Patients lacking mental capacity (i.e. patients suffering from dementia and others) to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Patients who meet all the eligibility criteria will be randomized 2:1 to receive treatment with either a BA9-DCB or a Sequent Please® Paclitaxel Coated Balloon.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biolimus A9™ Drug Coated Balloon<br>Patients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Biolimus A9™ Drug Coated Balloon | Device: Biolimus A9 Drug Coated Balloon<br>* A non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn.<br>|
| Active Comparator: Sequent ® Please Paclitaxel coated balloon<br>Patients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Sequent ® Please Paclitaxel coated balloon | Device: SeQuent Please Paclitaxel Drug Coated Balloon<br>* A non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Diameter Stenosis (DS) | Percent DS of the target segment assessed by quantitative coronary angiography (QCA) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target lesion failure | Taget lesion failure defined as a composite of cardiovascular death, any target vessel myocardial infarction, coronary artery bypass graft and clinically driven target lesion revascularization | 1 month, 6 months, 1 year and 2 years | 
| Target vessel failure | Target vessel failure defined as a composite of cardiovascular death, any target vessel myocardial infarction, and clinically driven target vessel revascularization | 1 month, 6 months, 1 year and 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-Coated Balloon