Surgical Implantation of TRAnscatheter vaLve in Native Mitral Annular Calcification (SITRAL) Study

Study Overview
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Brief Summary
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The purpose of this study is to establish the safety and feasibility of the Edwards SAPIEN 3 valve in subjects with mitral annular calcification (MAC) associated with mitral stenosis (MS) and/or mitral regurgitation who are at high-risk for mitral valve surgery or deemed inoperable due to the extent of calcification.

Detailed Description
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Technical Success: Alive, with Successful access, delivery and retrieval of the device delivery system, and Deployment and correct positioning (including repositioning/recapture if needed) of the single intended device, and No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure Device Success: Alive and stroke free, with Original intended device in place, and No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/Operating Room(OR)), and Intended performance of the device: Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = Mitral Valve Area (MVA) < 1.5cm2 and Mitral Valve (MV) gradient > 5mmHg, Insufficiency = Mitral Regurgitation (MR) >1+), and Absence of para-device complications (e.g., Paravalvular Leak (PVL) > mild, need for a Permanent Pacemaker (PPM), erosion, Annular rupture or Aortic Valve (AV) Groove disruption, Left Ventricular Outflow Tract (LVOT) gradient increase > 10mmHg) Procedural Success: Device success, and No device or procedure related Serious Adverse Events (SAEs) (Life threatening bleed; major vascular or cardiac structural complications requiring unplanned reintervention or surgery; stage 2 or 3 Acute Kidney Injury (includes new dialysis); Myocardial Infarction (MI) or need for percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG); severe heart failure (HF) or hypotension requiring intravenous (IV) inotrope, ultrafiltration or mechanical circulatory support; prolonged intubation ( > 48 hours) 6.2 Secondary objective(s) Device Success (at 6 months and 1 year) Subject success 1 year Device Success: Alive and stroke free, with Original intended device in place, and No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/Operating Room (OR)), and Intended performance of the device: Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = MVA < 1.5cm2 and MV gradient > 5mmHg, Insufficiency = MR >1+), and Absence of para-device complications (e.g., PVL > mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase > 10mmHg)

Official Title
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Surgical Implantation of TRAnscatheter vaLve in Native Mitral Annular Calcification (SITRAL) Study

Conditions
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Mitral Annular Calcification

Intervention / Treatment
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* Device: Mitral Valve Replacement with Sapien3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has severe native mitral annular calcification associated with mitral stenosis and/or regurgitation. Qualifying echo must be within 60 days of the date of the procedure. Subject has a clinical indication for mitral valve replacement, as demonstrated by reported New York Heart Association (NYHA) Functional Class II or greater. The subject is at least 22 years old. The Heart Team agrees that the subject is high risk or inoperable for surgical mitral valve repair or replacement (MVR), based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. The following concomitant procedures, are allowed: Maze, Tricuspid Valve Procedures (TVP), and Atrial Fibrillation (AF) ablation, coronary artery bypass grafting and septal myectomy. The study subject 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 subject agrees to comply with all required post-procedure follow-up visits Exclusion Criteria: Evidence of an acute myocardial infarction (MI) ≤ 30 days before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total creatine kinase (CK) elevation of creatine kinase-myocardial band (CK-MB) ≥ twice normal in the presence of myocardial band (MB) elevation and/or troponin level elevation (WHO definition)]. 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). Leukopenia (white blood cell count < 2000 cell/mL), acute anemia (hemoglobin < 8 g/dL), or thrombocytopenia (platelet count < 50,000 cell/mL). Hemodynamic or respiratory instability requiring vasoactive medications, mechanical ventilation at time of procedure. Need for emergency surgery for any reason. Severe left ventricular dysfunction with Left Ventricular Ejection Fraction (LVEF) < 30%. Severe right ventricular dysfunction Pregnancy, lactation, or planning to become pregnant Echocardiographic evidence of left ventricular mass, thrombus, or concerns of active infective endocarditis. Active upper gastrointestinal (GI) bleeding within 3 months prior to procedure without treatment or 30 days prior to procedure with definitive treatment. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be maintained on oral anticoagulant following the study procedure. End stage renal disease requiring dialysis Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 30 days of the procedure. Estimated life expectancy < 12 months

Ages Eligible for Study
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Minimum Age: 22 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: Mitral Valve Replacement with Sapien3<br>subjects with surgical MVR with Sapien3 | Device: Mitral Valve Replacement with Sapien3<br>* subjects with surgical MVR with Sapien3<br>* Other names: MVR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedural success | Procedural Success is defined as: Device success, and No device or procedure related serious adverse events (SAEs) (Life threatening bleed; major vascular or cardiac structural complications requiring unplanned reintervention or surgery; stage 2 or 3 acute kidney injury (AKI) (includes new dialysis); myocardial infarction (MI) or need for percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG); severe heart failure (HF) or hypotension requiring intravenous (IV) inotrope, ultrafiltration or mechanical circulatory support; prolonged intubation ( > 48 hours) | 30 days | 
| Technical success | Technical Success is defined as: Alive, with Successful access, delivery and retrieval of the device delivery system, and Deployment and correct positioning (including repositioning/recapture if needed) of the single intended device, and No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure | Procedure Stop Time | 
| Device success | Device Success is defined as: Alive and stroke free, with Original intended device in place, and No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/operating room (OR)), and Intended performance of the device: Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = mitral valve area (MVA) < 1.5cm2 and mitral valve (MV) gradient > 5mmHg, Insufficiency = mitral regurgitation (MR) >1+), and Absence of para-device complications (e.g., paravalvular leak (PVL) > mild, need for a permanent pacemaker (PPM), erosion, Annular rupture or aortic valve (AV) Groove disruption, left ventricular outflow tract (LVOT) gradient increase > 10mmHg) | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success | Device Success is defined as: Alive and stroke free, with Original intended device in place, and No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/operating room (OR)), and Intended performance of the device: Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = MVA < 1.5cm2 and MV gradient > 5mmHg, Insufficiency = MR >1+), and Absence of para-device complications (e.g., PVL > mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase > 10mmHg) | 6 months | 
| Device Success | Device Success is defined as: Alive and stroke free, with Original intended device in place, and No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/OR), and Intended performance of the device: Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = MVA < 1.5cm2 and MV gradient > 5mmHg, Insufficiency = MR >1+), and Absence of para-device complications (e.g., PVL > mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase > 10mmHg) | 1 year | 
| Subject success | Subject Success is defined as: All of the following must be present: I. Device success (either optimal or acceptable), and II. Patient returned to the pre-procedural setting: and III. No rehospitalizations or reinterventions for the underlying condition (e.g., mitral regurgitation, heart failure); and IV. Improvement from baseline in symptoms (e.g., NYHA improvement by > or = 1 functional class); and V. Improvement from baseline in functional status (e.g., 6-min walk test improvement by > or = 50 m); and VI. Improvement from baseline in quality-of-life (e.g., Kansas City Cardiomyopathy Questionnaire improvement by > or = 10) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mitral valve regurgitation, mitral valve stenosis