Beating Heart Mitral Valve Repair With the HARPOON™ System

Study Overview
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Brief Summary
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The objective of the study is to evaluate the safety and effectiveness of the HARPOON™ System in the treatment of patients with severe degenerative mitral regurgitation (DMR).

Detailed Description
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RESTORE is a prospective, multicenter, non-randomized trial designed to evaluate the safety and effectiveness of the HARPOON™ Beating Heart Mitral Valve Repair System in patients with severe degenerative mitral regurgitation (DMR).

Official Title
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A Prospective, Multi-center Trial to Evaluate the Safety and Effectiveness of Beating Heart Mitral Valve Repair With the HARPOON™ System (RESTORE)

Conditions
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Mitral Regurgitation

Intervention / Treatment
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* Device: HARPOON™ Beating Heart Mitral Valve Repair System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each subject is required to meet all of the following inclusion criteria: Patient is >/= 21 years old. Presence of severe degenerative mitral regurgitation with mid-segment posterior leaflet prolapse (without commissural involvement) by echocardiographic study. Mitral leaflet coaptation surface sufficient to reduce mitral regurgitation without undue leaflet tension, based on the judgment of the Echocardiographic Core Lab. Patient competent to sign informed consent and able to return for follow-up and is capable of participating in all testing associated with this clinical investigation. Exclusion Criteria: Patients will be excluded if ANY of the following criteria apply: Functional mitral regurgitation (FMR). Evidence of anterior or bileaflet prolapse. Severe mitral annular calcification (MAC). Moderate or greater leaflet calcification. Fragile or thinning apex (e.g. LV aneurysm). Have undergone cardiac or peripheral vascular procedures within 30 days prior to the trial procedure. Planned cardiac or peripheral vascular procedures within 30 days after the trial procedure. Requirement for concomitant cardiac surgery. Severe pulmonary hypertension (pulmonary artery systolic pressure > 60mmHg). Severe aortic stenosis or insufficiency. Severe tricuspid regurgitation. (Patients with mild or moderate tricuspid regurgitation are not excluded.) Left ventricular ejection fraction (LVEF) <30%, or severely impaired right ventricular dysfunction as measured by the core lab. Any history of endocarditis. Contraindication to cardiac surgery, including hostile chest or history of mediastinal radiation. Previous structural heart intervention (e.g. any heart valve replacement or repair procedures). Previous percutaneous coronary intervention (PCI) is allowed. Previous coronary artery bypass grafting (CABG). Stroke within 30 days prior to index procedure. ST segment elevation myocardial infarction (STEMI) requiring intervention within 30 days prior to index procedure. Evidence of cirrhosis or hepatic synthetic failure (Child-Pugh Class B or higher, [or MELD score of ≥ 13]). Renal insufficiency CKD Stage 3b or worse (GFR < 45 ml/min/1.73 m2). Hemodynamic instability or cardiogenic shock at the time of enrollment (e.g. requiring inotropic support or mechanical support devices). History of bleeding diathesis or coagulopathy or leukopenia (WBC < 3000 mcL) or acute anemia (Hb < 9 g/dL) or thrombocytopenia (platelets < 50,000 cells mcL). Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments (as assessed by Case Review Committee). Refuse blood products. Planned treatment with any other investigational device or procedure through 1-year follow-up, or who are currently participating in an investigational drug or device trial. Carotid stenosis ≥ to 80% at time of enrollment. Rheumatic heart disease including rheumatic mitral stenosis. Pregnant or lactating at the time of enrollment (women of childbearing age should have negative pregnancy test within 72 hours of surgery) or planning pregnancy within the next 12 months. Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator. Condition or conditions that, in the opinion of the Investigator, precludes participation, including willingness to comply with all follow-up procedures. Contraindication for transesophageal echocardiography (TEE), including esophageal spasm, esophageal stricture, esophageal laceration, esophageal perforation, esophageal diverticula (e.g. Zenker's diverticulum). Echocardiographic evidence of intracardiac mass (e.g. left ventricular, atrial, or appendage thrombus, myxoma, or vegetation). Cannot tolerate procedural anticoagulation or post-procedure antiplatelet regimen. Intra-operative exclusion criteria No longer meets eligibility criteria based on intra-operative assessment.

Ages Eligible for Study
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Minimum Age: 21 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HARPOON™ Beating Heart Mitral Valve Repair System<br>Subjects who were treated with the HARPOON™ Beating Heart Mitral Valve Repair System | Device: HARPOON™ Beating Heart Mitral Valve Repair System<br>* Repair of the chordae tendinae in the mitral valve.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Safety Endpoints | Composite safety endpoint, defined as freedom-from all-cause mortality, stroke, acute kidney injury (AKI), major bleeding, new permanent pace-maker implantation, deep sternal wound infection (DSWI) or wound infection requiring surgical intervention, and prolonged mechanical ventilation. | Discharge from the hospital or 30-days following the index procedure, whichever is longer. | 
| Composite Effectiveness Endpoints | Composite effectiveness endpoint, defined as freedom-from all-cause mortality, re-intervention on the mitral valve and recurrent [moderate or severe] MR. | 1 year following the index procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Product Usage | Blood product usage intraoperatively or post-operatively until discharge, in the HARPOON System treatment arm vs. open surgery. | Intraoperatively or post-operatively until discharge | 
| Procedure Time | Procedure time: first incision to incision close time in the HARPOON System treatment arm vs. open surgery. | First incision to incision close time | 
| OR Time | OR time: entry to OR suite and exit from OR suite in the HARPOON System treatment arm vs. open surgery. | Entry to OR suite and exit from OR suite | 
| Total Ventilation Hours | Total ventilation hours at discharge in the HARPOON System treatment arm vs. open surgery. | Discharge | 
| Total Hours in ICU | Total hours in the ICU post index procedure until discharge in the HARPOON System treatment arm vs. open surgery. | Post index procedure until discharge | 
| Percentage of subjects receiving mitral valve replacement (MVR) | Percentage of subjects receiving mitral valve replacement (MVR) during the index procedure in the HARPOON System treatment arm vs. open surgery. | During Index Procedure | 
| Hospital Length of Stay (LOS) | Hospital length of stay (LOS) post index procedure until discharge in the HARPOON System treatment arm vs. open surgery. | Post index procedure until discharge | 
| Composite Effectiveness Endpoint | Composite effectiveness endpoint, defined as freedom from all-cause mortality, re-intervention on the mitral valve and recurrent (moderate or severe) mitral regurgitation (MR) for one year following the index procedure, in the HARPOON System treatment arm vs. CTSN-TR comparator. | One year following the index procedure | 
| Discharged to Home vs. Other Facility | Discharged to home vs. other facility, in the HARPOON System treatment arm vs. open surgery. | Discharge |