The MITRAL II Pivotal Trial (Mitral Implantation of TRAnscatheter vaLves).

Study Overview
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Brief Summary
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A prospective multicenter study enrolling high surgical risk patients with severe mitral annular calcification (MAC) and symptomatic mitral valve disease. There are 2 arms in this study: Transseptal Valve-in-MAC (ViMAC) and a control arm of patients treated with medical treatment only which will include patients who can't be treated due to the presence of anatomical exclusion criteria or other exclusion criteria.

Detailed Description
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STUDY OBJECTIVE The purpose of this study is to establish the safety and effectiveness of the Edwards SAPIEN 3 and SAPIEN 3 Ultra valves with Commander delivery system in patients with severe symptomatic calcific mitral valve disease with severe mitral annular calcification who are not candidates for standard mitral valve surgery. STUDY DESIGN A prospective multicenter study enrolling high surgical risk patients with severe mitral annular calcification (MAC) and symptomatic mitral valve disease. There are 2 arms in this study: Transseptal Valve-in-MAC (ViMAC) and a control arm of patients treated with medical treatment only which will include patients who can't be treated due to the presence of anatomical exclusion criteria or other exclusion criteria. Enrollment Enrollment will consist of 110 patients in the treatment arm (transseptal ViMAC) and up to 100 in the medically treated arm).

Official Title
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The Safety and Effectiveness of the SAPIEN 3 and SAPIEN 3 Ultra Valve in Patients With Symptomatic Severe Calcific Mitral Valve Disease With Severe Mitral Annular Calcification Who Are Not Candidates for Standard Mitral Valve Surgery.

Conditions
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Mitral Annular Calcification, Mitral Stenosis, Mitral Regurgitation, Mitral Valve Disease

Intervention / Treatment
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* Device: Transseptal ViMAC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Candidates must meet the following criteria: - 18 years of age or older -Severe mitral annular calcification with severe mitral stenosis defined as mitral valve area (MVA) of ≤1.5 cm2, or moderate to severe or severe mitral regurgitation. - NYHA Functional Class ≥II. The heart team agrees that valve implantation will likely benefit the patient. High or prohibitive risk for standard mitral valve surgery as determined by the heart team (at least one site cardiac surgeon must personally examine the subject to determine operative risk). The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site. The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up. Exclusion Criteria: - The heart team considers the patient is a surgical candidate. - Mitral annulus is not calcified. - Myocardial infarction requiring revascularization within 30 days from procedure. - Clinically significant untreated coronary artery disease requiring revascularization. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease). Implantation of a permanent pacemaker is not excluded. Any patient with a balloon valvuloplasty (BMV) within 30 days of the procedure (unless BMV is a bridge to procedure after a qualifying Echo). Severe symptomatic tricuspid regurgitation (hepatic dysfunction, ascites, edema not controlled with diuretics) requiring surgery. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Platelets < 50,000 cell/mL), history of coagulopathy or hypercoagulable state. Hypertrophic obstructive cardiomyopathy (HOCM) with mean LVOT gradient of ≥20 mm Hg at rest or ≥50 mmHg with Valsalva. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation. Need for emergency surgery for any reason. Severe left ventricular dysfunction with LVEF < 20%. Echocardiographic evidence of intracardiac mass, thrombus or vegetation. Active upper GI bleeding within 90 days prior to procedure. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure. Cardiac anatomy that would preclude appropriate delivery and deployment of a SAPIEN 3 or SAPIEN 3 Ultra valve in MAC via transseptal access, including but not limited to: Native neo mitral annulus size < 275 mm2 or > 810 mm2 as measured by CT scan. Significant risk of LVOT obstruction or valve embolization as assessed by CT core lab Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 90 days of the procedure. Estimated life expectancy <12 months due to non-cardiac conditions. Expectation that patient will not improve despite treatment of mitral valve dysfunction. Active bacterial endocarditis within 180 days of procedure. - Severe right ventricular dysfunction as assessed by Echo core lab - Active infection requiring antibiotic therapy (subject may be a candidate after 2 weeks of antibiotic discontinuation. - Female who is pregnant or lactating. - Participating in another investigational device study. - Aortic valve disease requiring intervention. - Severe fixed pulmonary hypertension (PASP ≥70 mmHg). - Severe chronic obstructive pulmonary disease requiring continuous home oxygen. - The patient refuses mitral valve intervention - Recent symptomatic COVID-19 infection with residual symptoms that may affect the outcomes of this trial.

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: Parallel Assignment
Interventional Model Description: 210 subjects: 110 in treatment arm and 100 in registry of medical treatment for patients who are not eligible for treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transseptal ViMAC<br>110 MAC patients treated with transseptal Valve-in-MAC. | Device: Transseptal ViMAC<br>* Transseptal TMVR using balloon-expandable aortic transcatheter valves.<br>* Other names: ViMAC;|
| No Intervention: Registry of untreated patients<br>100 MAC patients not eligible for transseptal ViMAC, treated with conservative management including medications. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoint: All Cause Morality and Hospitalization for Heart Failure | A non-hierarchical composite of all-cause mortality and hospitalization for heart failure. | 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Effectiveness Endpoint | • Stroke at 30 days and 1 year. | 1 year | 
| Secondary Effectiveness Endpoint | • Change from baseline in New York Heart Association Class at 1 year. | 1 year. | 
| Secondary Effectiveness Endpoint | • Change from baseline in distance walked measure by the 6 Minute Walk Test at 1 year. | 1 year. | 
| Secondary Effectiveness Endpoint | • Change from baseline in quality of life measure by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 1 year. | 1 year. | 
| Secondary Effectiveness Endpoint | • Echocardiographic assessment of degree of mitral regurgitation (central and paravalvular) at 1 year. | 1 year. | 
| Secondary Effectiveness Endpoint | • Significant mitral stenosis defined as mean mitral valve gradient by echo > 10 mmHg at 1 year. | 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter Mitral Valve Replacement