Mitral Annular Calcification
Conditions
Keywords
mitral valve regurgitation, mitral valve stenosis
Brief summary
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
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)
Interventions
DEVICEMitral Valve Replacement (MVR) with Sapien3
subjects with surgical MVR with Sapien3
Sponsors
Edwards Lifesciences
Baylor Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Procedural Success | 30 days | Procedural Success is defined as: 1. Device success, and 2. 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) |
| Technical Success | Procedure Stop Time | Technical Success is defined as: 1. Alive, with 2. Successful access, delivery and retrieval of the device delivery system, and 3. Deployment and correct positioning (including repositioning/recapture if needed) of the single intended device, and 4. No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure |
| Device Success | 30 days | Device Success is defined as: 1. Alive and stroke free, with 2. Original intended device in place, and 3. 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 4. Intended performance of the device: 1. Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and 2. 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 3. 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Device Success | 6 months | Device Success is defined as: 1. Alive and stroke free, with 2. Original intended device in place, and 3. 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 4. Intended performance of the device: 1. Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and 2. 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 3. Absence of para-device complications (e.g., PVL \> mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase \> 10mmHg) |
| Subject Success | 1 year | 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) |
Countries
United States
Participant flow
Recruitment details
This was a prospective, open-label, multicenter study which identified participants from 8 participating institutions, with 6 different study sites enrolling participants into the trial. First participant enrollment took place on 11/04/2016 with the final participant enrolled on 08/05/2022. All participants were followed for 12 months with the final participant visit taking place on 11/29/2023.
Pre-assignment details
All participants potentially eligible participants are presented via a case review process where experienced study investigators reviewed all the submitted criteria. Upon case review approval the participant can be enrolled in the study. All approved participants receive the Edwards SAPIEN 3 valve placed in the mitral valve position.
Participants by arm
| Arm | Count |
|---|---|
| Mitral Valve Replacement With SAPEIN3 Subjects with surgical Mitral Valve Replacement with SAPEIN3 using minimally invasive surgical technique. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 9 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Mitral Valve Replacement With SAPEIN3 | — |
|---|---|---|
| Age, Continuous | 75.6 years STANDARD_DEVIATION 7.1 | — |
| Arrythmia | 11 Participants | — |
| Body mass index (BMI) | 29.63 kg/m^2 STANDARD_DEVIATION 5.7 | — |
| Concomitant Aortic Valvular Disease | 17 Participants | — |
| Congestive Heart Failure | 12 Participants | — |
| Diabetes | 11 Participants | — |
| Diffusing Capacity for Carbon Monoxide (DLCO%) | 56.50 Percentage STANDARD_DEVIATION 23.3 | — |
| Forced expiratory volume in 1 second (FEV1%) | 63.47 Percentage STANDARD_DEVIATION 26.93 | — |
| Hyperlipidemia | 19 Participants | — |
| Hypertension | 16 Participants | — |
| New York Heart Association (NYHA) Classification | 2.84 units on a scale STANDARD_DEVIATION 0.69 | — |
| Prior Cardiac Intervention | 16 Participants | — |
| Prior Myocardial Infarction (MI) | 5 Participants | — |
| Pulmonary Disease | 10 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 20 Participants | — |
| Sex: Female, Male Male | 5 Participants | — |
| Society of Thoracic Surgeons (STS) Risk of Mortality Mitral Valve Repair | 4.00 Percentage STANDARD_DEVIATION 2.57 | — |
| Society of Thoracic Surgeons (STS) Risk of Mortality Mitral Valve Replacement | 6.13 Percentage STANDARD_DEVIATION 2.84 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 25 |
| other Total, other adverse events | 24 / 25 |
| serious Total, serious adverse events | 20 / 25 |
Outcome results
Primary
Device Success
Device Success is defined as: 1. Alive and stroke free, with 2. Original intended device in place, and 3. 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 4. Intended performance of the device: 1. Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and 2. 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 3. 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)
Time frame: 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mitral Valve Replacement With SAPEIN3 | Device Success | Known met Outcome Measure | 0 Participants |
| Mitral Valve Replacement With SAPEIN3 | Device Success | Unknown | 12 Participants |
| Mitral Valve Replacement With SAPEIN3 | Device Success | Did not meet Outcome Measure | 13 Participants |
Primary
Procedural Success
Procedural Success is defined as: 1. Device success, and 2. 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)
Time frame: 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mitral Valve Replacement With SAPEIN3 | Procedural Success | Met Outcome Measure | 16 Participants |
| Mitral Valve Replacement With SAPEIN3 | Procedural Success | Did Not Meet Outcome Measure | 9 Participants |
Primary
Technical Success
Technical Success is defined as: 1. Alive, with 2. Successful access, delivery and retrieval of the device delivery system, and 3. Deployment and correct positioning (including repositioning/recapture if needed) of the single intended device, and 4. No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure
Time frame: Procedure Stop Time
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mitral Valve Replacement With SAPEIN3 | Technical Success | Met Outcome Measure | 21 Participants |
| Mitral Valve Replacement With SAPEIN3 | Technical Success | Did Not Meet Outcome Measure | 4 Participants |
Secondary
Device Success
Device Success is defined as: 1. Alive and stroke free, with 2. Original intended device in place, and 3. 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 4. Intended performance of the device: 1. Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and 2. 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 3. Absence of para-device complications (e.g., PVL \> mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase \> 10mmHg)
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mitral Valve Replacement With SAPEIN3 | Device Success | Known Met Outcome Measure | 0 Participants |
| Mitral Valve Replacement With SAPEIN3 | Device Success | Unknown | 11 Participants |
| Mitral Valve Replacement With SAPEIN3 | Device Success | Known Did Not Meet Outcome Measure | 14 Participants |
Secondary
Device Success
Device Success is defined as: 1. Alive and stroke free, with 2. Original intended device in place, and 3. 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 4. Intended performance of the device: 1. Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and 2. 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 3. Absence of para-device complications (e.g., PVL \> mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase \> 10mmHg)
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mitral Valve Replacement With SAPEIN3 | Device Success | Known Met Outcome Measure | 2 Participants |
| Mitral Valve Replacement With SAPEIN3 | Device Success | Unknown | 10 Participants |
| Mitral Valve Replacement With SAPEIN3 | Device Success | Known Did Not Meet Outcome Measure | 13 Participants |
Secondary
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)
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mitral Valve Replacement With SAPEIN3 | Subject Success | Unknown | 10 Participants |
| Mitral Valve Replacement With SAPEIN3 | Subject Success | Known Met Outcome Measure | 0 Participants |
| Mitral Valve Replacement With SAPEIN3 | Subject Success | Known Did Not Meet Outcome Measure | 15 Participants |