EXPLORE FMR: Early Feasibility Study of the PLAR Implant and Delivery System to Treat Functional Mitral Regurgitation

Study Overview
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Brief Summary
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An early feasibility study to evaluate the safety and feasibility of the PLAR Implant and Delivery System to treat severe functional mitral regurgitation and to gather preliminary data on its performance thereby providing guidance for future clinical development. The study is a single-arm registry with the last follow-up visit at 5 years post-intervention. The study will enroll up to 10 patients at one (1) center in Brazil.

Detailed Description
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Percutaneous approaches to treat MR promise to provide a sufficient reduction in MR without the risks typically associated with open heart surgery. Furthermore there is an unmet clinical need for patients with severe MR who are refused or denied surgery due to high risk. Percutaneous therapy provides a novel alternative treatment option for these patients with the aim of reducing morbidity and mortality over and above current medical therapy. The Polares Medical PLAR Implant and Delivery System is a catheter-based technology designed to permanently implant a prosthesis using a transvenous / transseptal approach to augment the posterior mitral valve leaflet and improve coaptation with the anterior leaflet. Approved edge-to-edge repair has already been shown to be a viable alternative for high risk MR patients. However treatment with these devices is limited to specific anatomies and often requires multiple devices which increases clinical risk, adds to procedural time, and can result in residual MR. The PLAR Implant and Delivery System has been designed to overcome and mitigate some of these shortfalls.

Official Title
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Early Feasibility Study of the PLAR Implant and Delivery System to Treat Functional Mitral Regurgitation (EXPLORE FMR)

Conditions
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Functional Mitral Regurgitation

Intervention / Treatment
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* Device: Transcatheter mitral valve repair (PLAR Implant and Delivery System)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Greater than moderate 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), but operable, 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 New York Heart Association (NYHA) Functional Class III or IV Patient willing to participate in study and provide signed IRB/EC-approved informed consent Treating physician and patient agree that patient is able to return for all required post-procedure follow-up visits 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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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Single-arm registry
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-arm study of PLAR Implant and Delivery System<br>All enrolled patients will receive the study device | Device: Transcatheter mitral valve repair (PLAR Implant and Delivery System)<br>* The PLAR Implant is placed on the mitral valve posterior annulus using its delivery system via femoral vein access and a transeptal puncture<br>* Other names: TMVr;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of all-cause mortality | Primary safety outcome | 30-days follow-up | 
| Incidence of change from baseline to moderate or less mitral regurgitation (Grade 2+ or less) as evaluated by 2D TTE Primary performance endpoint | Primary performance endpoint | 30-days follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major safety events as defined by MVARC2 definitions | Secondary safety endpoint | Follow-up at 30 days, at 6 and 12 months, and at 2, 3, 4 and 5 years | 
| Technical success rate per MVARC2 definitions | All of the following must be present for technical success: 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 | Technical success is measured immediately following the procedure | 
| Procedure success rate per MVARC2 definitions | Both of the following must be present for procedure success: Device success Absence of major device or procedure-related serious adverse events as below: Death Stroke Life-threatening bleed Major vascular complication Major cardiac structural complication 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 | Procedure success is measured at 30 days follow-up | 
| Device success rate per MVARC 2 definitions | All of the following must be present for device success: 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 as below: No evidence of structural or functional failure No device technical failure issues/complications MR reduction to moderate or less without stenosis | Device success is measured at 30 days, at 6 and 12 months, and at 2, 3, 4, and 5 years follow-up | 
| Patient success rate per MVARC2 definitions | All of the following must be present for patient success: 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 | Patient success is measured at 12 months follow-up |