The ENCIRCLE Trial

Study Overview
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Brief Summary
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This study will establish the safety and effectiveness of the SAPIEN M3 System in subjects with symptomatic, at least 3+ mitral regurgitation (MR) for whom commercially available surgical or transcatheter treatment options are deemed unsuitable. Following completion of enrollment, subjects will be eligible for enrollment in the continued access phase of the trial.

Detailed Description
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This is a prospective single-arm, multicenter study.

Official Title
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SAPIEN M3 System Transcatheter Mitral Valve Replacement Via Transseptal Access

Conditions
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Mitral Regurgitation, Mitral Valve Insufficiency

Intervention / Treatment
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* Device: SAPIEN M3 valve and dock


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older MR ≥ 3+ NYHA functional class ≥ II Per the Heart Team, commercially available surgical or transcatheter treatment options are deemed unsuitable due to clinical, anatomic or technical considerations. Subject's heart failure management has been optimized based on subject characteristics and applicable guidelines, and stable for at least 30 days prior to enrollment. The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent. Exclusion Criteria: Mitral/cardiac anatomy that would preclude appropriate delivery and deployment of the SAPIEN M3 dock or valve Inappropriate anatomy for femoral introduction and delivery of the SAPIEN M3 dock and valve Presence of any device that will contact or interfere with the SAPIEN M3 System during delivery or after implantation Left ventricular ejection fraction <25% Severe right ventricular dysfunction Need for aortic, tricuspid or pulmonic valve intervention within the next 12 months History of heart transplant Cardiac imaging evidence of intracardiac mass, thrombus or vegetation Active bacterial endocarditis within 180 days of the procedure Hemodynamic instability requiring inotropic or mechanical support within 30 days of the procedure Myocardial infarction within 30 days of the procedure Clinically significant untreated coronary artery disease requiring revascularization Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 30 days of the procedure Stroke or transient ischemic attack within 90 days of the procedure Irreversible, severe pulmonary hypertension Chronic obstructive pulmonary disease requiring home oxygen therapy or chronic outpatient oral steroid use Renal insufficiency or receiving renal replacement therapy Liver disease Planned surgery within the next 12 months Inability to tolerate or a medical condition precluding treatment with antithrombotic therapy, including heparin administration during the procedure Active infection requiring current antibiotic therapy Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy or hypercoagulable states Refusal of blood products Female who is pregnant or lactating Estimated life expectancy <12 months due to non-cardiac conditions Participating in another investigational drug or device study that has not reached its primary endpoint Subject considered to be part of a vulnerable population

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMVR - Main Cohort<br>Subjects for whom commercially available surgical or transcatheter treatment options are deemed unsuitable will have transcatheter mitral valve replacement (TMVR). | Device: SAPIEN M3 valve and dock<br>* During the procedure a SAPIEN M3 dock and a SAPIEN M3 valve will be implanted via transseptal approach.<br>|
| Experimental: TMVR - Failed TEER Registry<br>Subjects who have had an attempted but failed transcatheter edge-to-edge repair (TEER) procedure will have TMVR. | Device: SAPIEN M3 valve and dock<br>* During the procedure a SAPIEN M3 dock and a SAPIEN M3 valve will be implanted via transseptal approach.<br>|
| Experimental: TMVR - MAC Registry<br>Subjects with mitral annular calcification (MAC) will have TMVR. | Device: SAPIEN M3 valve and dock<br>* During the procedure a SAPIEN M3 dock and a SAPIEN M3 valve will be implanted via transseptal approach.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-hierarchical composite of death and heart failure rehospitalization | Number of subjects with death and/or heart failure rehospitalization | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in NYHA functional class compared to baseline | New York Heart Association (NYHA) functional classification of heart failure is based on how much a patient is limited during physical activity. The rating ranges from I-IV. I = no limitations of physical activity; II = slight limitations of physical activity, ordinary physical activity results in fatigue, palpitation, shortness of breath; III = marked limitations of physical activity, less than ordinary activity causes fatigue, palpitation, or shortness of breath; IV = unable to carry on any physical activity without discomfort, symptoms of heart failure at rest. | 1 year | 
| Improvement in KCCQ Overall Score compared to baseline | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | 1 year | 
| Improvement in MR compared to baseline | Number of subjects with improved MR compared to baseline | 1 year | 
| Decrease in LVEDVi compared to baseline | Number of subjects with decreased left ventricular end-diastolic volume index (LVEDVi) compared to baseline | 1 year |