ALLIANCE Mitral: Safety and Effectiveness of SAPIEN X4 Transcatheter Heart Valve - Mitral

Study Overview
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Brief Summary
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This study will establish the safety and effectiveness of the Edwards SAPIEN X4 Transcatheter Heart Valve (THV) in subjects who are at high or greater surgical risk with a failing mitral surgical bioprosthetic valve or a failing native mitral valve with an annuloplasty ring.

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

Official Title
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Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve - Mitral

Conditions
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Mitral Regurgitation, Mitral Valve Disease, Mitral Stenosis

Intervention / Treatment
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* Device: SAPIEN X4 THV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Failing mitral surgical bioprosthetic valve or a failing native mitral valve with an annuloplasty ring demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency Bioprosthetic surgical valve or native mitral annulus size suitable for SAPIEN X4 THV NYHA functional class ≥ II Heart Team agrees the subject is at high or greater surgical risk The subject has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent. Exclusion Criteria: Anatomical characteristics that would preclude safe femoral placement of the introducer sheath or safe passage of the delivery system Interatrial septum or left atrium not suitable for transcatheter transseptal access Failing valve has mild or greater paravalvular regurgitation Failing valve is unstable, rocking, or not structurally intact Annuloplasty ring dehiscence Known severe patient-prosthesis mismatch or bioprosthetic valve with residual mean gradient > 10 mmHg at the end of the index procedure for implantation of the original valve Annuloplasty ring type not favorable for THV implantation Increased risk of THV embolization Anatomical characteristics that would increase risk of left ventricular outflow tract (LVOT) obstruction Surgical or transcatheter aortic valve extending into LVOT that may impinge on the mitral implant Severe right ventricle (RV) dysfunction Severe regurgitation or stenosis of any other valve Need for aortic, tricuspid, or pulmonic valve intervention within the next 12 months Left ventricular ejection fraction < 20% Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation Myocardial infarction within 30 days prior to the study procedure Hypertrophic cardiomyopathy with subvalvular obstruction Subjects with planned concomitant ablation for atrial fibrillation Clinically significant coronary artery disease requiring revascularization Any surgical or transcatheter procedure within 30 days prior to the study procedure. Implantation of a permanent pacemaker or implantable cardioverter defibrillator (ICD) is not considered an exclusion. Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure Endocarditis within 180 days prior to the study procedure Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure Renal insufficiency and/or renal replacement therapy Leukopenia, anemia, thrombocytopenia Inability to tolerate or condition precluding treatment with antithrombotic therapy Hypercoagulable state or other condition that increases risk of thrombosis Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication Subject refuses blood products Body mass index > 50 kg/m2 Estimated life expectancy < 24 months Female who is pregnant or lactating Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments Participating in another investigational drug or device study that has not reached its primary endpoint Subject considered to be part of a vulnerable population
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 in failing mitral surgical bioprosthetic valve<br>Transcatheter Mitral Valve Replacement (TMVR) in subjects with a failing mitral surgical bioprosthetic valve. | Device: SAPIEN X4 THV<br>* Implantation of the SAPIEN X4 valve<br>|
| Experimental: TMVR in failing native mitral valve with an annuloplasty ring<br>Transcatheter Mitral Valve Replacement (TMVR) in subjects with a failing native mitral valve with an annuloplasty ring. | Device: SAPIEN X4 THV<br>* Implantation of the SAPIEN X4 valve<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 stroke at 1 year | The number of patients that died or had a stroke | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to baseline | The 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. | 30 days | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to baseline | The 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 | 
| New York Heart Association (NYHA) functional class compared to baseline | NYHA is a functional classification of heart failure based on how much a patient is limited during physical activity. The rating ranges from I - IV, with the lowest (I) as no limitations and the highest (IV) unable to carry on any physical activity without discomfort. | 30 days | 
| New York Heart Association (NYHA) functional class compared to baseline | NYHA is a functional classification of heart failure based on how much a patient is limited during physical activity. The rating ranges from I - IV, with the lowest (I) as no limitations and the highest (IV) unable to carry on any physical activity without discomfort. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SAPIEN X4, Valve-in-Valve, Valve-in-Ring