Early Feasibility EXperience of Posterior Leaflet RestOration to REduce Mitral Regurgitation

Study Overview
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Brief Summary
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Early feasibility study, single-arm registry design

Detailed Description
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First-In-Human

Official Title
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Early Feasibility EXperience of Posterior Leaflet RestOration to REduce Mitral Regurgitation (EXPLORE MR)

Conditions
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Mitral Regurgitation, Mitral Valve Disease, Mitral Valve Insufficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older. Greater than moderate degenerative or functional mitral regurgitation (Grade 3+ or higher) as confirmed by transesophageal echocardiography (TEE) within 90 days prior to study procedure Patient must present with an STS Score less than 10% High surgical risk for conventional mitral repair or replacement due to morphological criteria (e.g. leaflet or annulus calcifications) as assessed by the local heart team comprised of a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in treating mitral valve disease and heart failure Mitral valve anatomy deemed unsuitable to be treated with an approved edge-to-edge repair system (e.g., retracted posterior leaflet, lack of leaflet tissue, calcified or cleft posterior leaflet) as assessed by the local heart team comprised of a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in treating mitral valve disease and heart failure Patient is approved by an independent Patient Eligibility Committee New York Heart Association (NYHA) Functional Class III or IV Patient willing to participate in study and provide signed EC-approved informed consent. Treating physician and patient agree that patient is able to return for all required post- procedure follow-up visits Women of child-bearing potential have a negative pregnancy test Exclusion Criteria: Severe tricuspid regurgitation Severe aortic stenosis or insufficiency Severe mitral annulus calcification Diseased mitral anterior leaflet such as flail / prolapse/ heavy calcification Implanted vena cava filter Femoral veins with severe angulation and calcification Contraindication for transesophageal echocardiography (TEE) or MDCT scan. Active infection or endocarditis Previous mitral valve surgery Prior orthotopic heart transplantation Pulmonary artery systolic hypertension > 70mmHg Evidence of intra-cardiac, inferior vena cava (IVC) or femoral venous thrombus Left ventricular ejection fraction (LVEF) < 30% Implant or revision of any pacing device < 30 days prior to intervention Symptomatic coronary artery disease treated < 30 days prior to study procedure Myocardial infarction requiring intervention < 30 days prior to study procedure Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis), hypertrophic or restrictive cardiomyopathies, and constrictive pericarditis Active peptic ulcer or upper gastrointestinal bleeding < 90 days prior to study procedure Stroke < 180 days prior to study procedure Severe renal insufficiency (creatinine > 3.0 mg/dL) or patient requiring dialysis Cardiogenic shock at time of enrolment Hemodynamic instability requiring inotropic support or mechanical heart assistance Concurrent medical condition with a life expectancy of less than 2 years Pregnancy at time of enrolment History of bleeding diathesis or coagulopathy or leukopenia (WBC < 3,000 mcL) or acute anemia (Hb < 9 g/dL) or thrombocytopenia (platelets < 50,000 cells mcL) Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine or clopidogrel, nitinol, tantalum or allergy to contrast agents that cannot be pre-medicated Severe dementia or lack of capacity due to conditions that result in either inability to provide informed consent for the trial/procedure, prevent independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up assessments Emergency situations Company employees or their immediate family members Patient is under guardianship Patient is participating in another clinical study for which follow-up is currently ongoing

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary safety endpoint | All-cause mortality | 30 days | 
| Improvement from baseline mitral regurgitation | Grade 2+ or less as evaluated by 2D transthoracic echocardiography | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success according to MVARC2 criteria | Absence of procedure mortality Successful access, delivery and retrieval of investigation delivery system Successful deployment and correct positioning of intended implant(s) Freedom from emergency surgery/re-intervention related to device or access procedure | 24 hours | 
| Procedure success according to MVARC2 criteria | Absence of procedure mortality or stroke Proper placement and positioning of device Freedom from unplanned re-intervention related to device or access procedure Continued intended safety and performance of the device: No evidence of structural or functional failure No device technical failure issues/complications MR reduction to moderate or less without stenosis Absence of major device or procedure-related SAE: Death Stroke Life-threatening bleed Major vascular complication Major cardiac structural complication No device technical failure issues/complications Stage 2 or 3 AKI MI or coronary ischemia requiring PCI or CABG Shock, heart or respiratory failure requiring IV vasopressors, mechanical intervention or prolonged intubation Valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention | 30 days | 
| Device success according to MVARC2 criteria | Absence of procedure mortality or stroke Proper placement and positioning of device Freedom from unplanned re-intervention related to device or access procedure Continued intended safety and performance of the device: No evidence of structural or functional failure No device technical failure issues/complications MR reduction to moderate or less without stenosis | 30 days, 6 and 12 months, and 2 - 5 years post treatment | 
| Patient success according to MVARC2 criteria | Device success Patient returned to pre-procedure setting No rehospitalization or reintervention for mitral regurgitation or heart failure Functional improvement from baseline by one or more NYHA class 6MWT improvement from baseline by 50 metres or more | 30 days, 6 and 12 months, and 2 - 5 years post treatment | 
| Rate (%) of major adverse events as defined by MVARC2 criteria | All-cause mortality, hospitalization due to cardiac conditions, stroke or TIA, myocardial infarction, access site and vascular complications, bleeding complications, acute kidney injury up to 7 days post-procedure, and arrhythmias and conduction system disturbances | Procedure, discharge/7 days, 30 days, 6 and 12 months, and 2 - 5 years post treatment |