Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation

Study Overview
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Brief Summary
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Prospective, controlled, multicenter clinical investigation with four trial cohorts: Randomized, Non-repairable, Severe Mitral Annular Calcification (MAC) and Severe Mitral Annular Calcification Continued Access Protocol (MAC CAP). Subjects in the Randomized cohort will be randomized in a 1:1 ratio to the trial device or to the MitraClip system. Subjects in the Non-repairable, Severe MAC, and Severe MAC CAP cohorts will receive the trial device. The objective of the Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation (SUMMIT) is to evaluate the safety and effectiveness of the Tendyne Transcatheter Mitral Valve System for the treatment of patients with symptomatic, moderate-to-severe or severe mitral regurgitation or for patients with symptomatic mitral valve disease due to severe mitral annular calcification. This randomized controlled trial will provide the opportunity to evaluate the safety and clinical benefits of the Tendyne Transcatheter Mitral Valve System compared to the MitraClip System in patients with symptomatic, moderate-to-severe or severe mitral regurgitation, within approved MitraClip indications. In addition, the safety and effectiveness of the Tendyne Transcatheter Mitral Valve System will be evaluated in patients with severe mitral annular calcification who are at prohibitive risk for mitral valve surgery. Patients who are not suitable for mitral valve surgery for reasons other than severe mitral annular calcification and are also not suitable for transcatheter repair with MitraClip, will be enrolled in the Non-repairable cohort. Subjects will be seen at screening, pre- and post-procedure, discharge, 30 days, 3 months, 6 months, and annually through 5 years.

Official Title
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Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation

Conditions
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Mitral Regurgitation, Mitral Insufficiency, Mitral Valve Insufficiency, Cardiovascular Diseases, Valve Disease, Heart, Heart Valve Diseases, Functional Mitral Regurgitation, Degenerative Mitral Valve Disease

Intervention / Treatment
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* Device: Tendyne Mitral Valve System
* Device: MitraClip System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic, moderate-to-severe or severe mitral regurgitation, or severe mitral annular calcification (MAC) NYHA Functional Classification ≥ II (if Class IV, patient must be ambulatory) The local site heart team determines that the subject has been adequately treated per applicable standards Not a member of a vulnerable population Exclusion Criteria: Mitral valvular vegetation or mass Left ventricular ejection fraction < 25% Left ventricular end diastolic diameter > 7.0 cm Prior surgical or interventional treatment of mitral valve involving implantation of prosthetic material Aortic valve disease requiring surgery or transcatheter intervention Severe tricuspid regurgitation or any tricuspid valve disease requiring surgery or transcatheter intervention Any planned surgical / interventional procedure within 60 day prior to or following subject randomization Subject undergoing hemodialysis due to chronic renal failure Mitral pathoanatomy and left ventricular outflow tract anatomy deemed not suitable for Trial device implantation Subjects with non-cardiac comorbidities that are likely to result in a life expectancy of less than 12 months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Cohort - Treatment Group<br>Treatment of mitral regurgitation with the Tendyne Transcatheter Mitral Valve System | Device: Tendyne Mitral Valve System<br>* Mitral valve replacement<br>|
| Active Comparator: Randomized Cohort - Control Group<br>Treatment of mitral regurgitation within commercially approved MitraClip system indications | Device: MitraClip System<br>* Percutaneous mitral valve repair using the MitraClip system.<br>|
| Experimental: Non-repairable Cohort<br>Treatment of mitral regurgitation with the Tendyne Transcatheter Mitral Valve System | Device: Tendyne Mitral Valve System<br>* Mitral valve replacement<br>|
| Experimental: Severe Mitral Annular Calcification (MAC) Cohort<br>Treatment of mitral regurgitation and mitral annular calcification with the Tendyne Transcatheter Mitral Valve System | Device: Tendyne Mitral Valve System<br>* Mitral valve replacement<br>|
| Experimental: Severe Mitral Annular Calcification Continued Access Protocol (MAC CAP) Cohort<br>Treatment of mitral regurgitation and mitral annular calcification with the Tendyne Transcatheter Mitral Valve System after the completion of enrollment in the Severe MAC Cohort | Device: Tendyne Mitral Valve System<br>* Mitral valve replacement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Randomized Cohort | Survival free of heart failure hospitalization at 12 months post index procedure | 1 year | 
| Non-repairable Cohort | Survival free of heart failure hospitalization at 12 months post index procedure | 1 year | 
| Severe Mitral Annular Calcification (MAC) Cohort | Survival free of heart failure hospitalization at 12 months post index procedure | 1 year | 
| Severe MAC Continued Access Protocol (MAC CAP) Cohort | Survival free of heart failure hospitalization at 12 months post index procedure | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in distance walked, as measured by the 6 Minute Walk Test (6MWT) |  | 1 year | 
| Change from baseline in quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) |  | 1 year | 
| Change from baseline in health outcomes, as measured by the EQ-5D |  | 1 year | 
| • Change from baseline in health outcomes, as measured by the 12-item Short Form Health Survey (SF-12) |  | 1 year | 
| Change from baseline in New York Heart Association Classification |  | 1 year |