Heart Failure, Mitral Valve Disease, Mitral Valve Insufficiency, Mitral Valve Regurgitation
Conditions
Keywords
SAPIEN 3, PARTNER 3, cardiovascular disease, TMVR, failing valve, failing bioprosthetic valve
Brief summary
To assess the safety and effectiveness of the SAPIEN 3 transcatheter heart valve in patients with a failing mitral bioprosthetic valve.
Detailed description
A prospective, single-arm, multicenter clinical trial. This study will enroll patients with symptomatic heart disease due to a failing bioprosthetic mitral valve (stenosed, insufficient, or combined).
Interventions
DEVICEEdwards SAPIEN 3 transcatheter valve, Model 9600TFX
Edwards SAPIEN 3 THV system Model 9600TFX with the associated delivery systems.
Sponsors
Edwards Lifesciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Failing surgically implanted bioprosthetic valve in the mitral position demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency. 2. Surgical bioprosthetic valve with a true internal diameter (True ID) of 16.5 mm to 28.5 mm. 3. NYHA Functional Class ≥ II. 4. Heart Team agrees the patient is intermediate risk (i.e. STS score of ≥3 and \< 8). 5. Heart Team agrees valve implantation will likely benefit the patient. 6. 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) / Ethics Committee (EC) of the respective clinical site.
Exclusion criteria
1. Index valve has ≥ mild paravalvular regurgitation where the surgical bioprosthesis is not securely fixed in the native annulus or is not structurally intact as determined by transesophageal echocardiography (TEE). 2. Surgical or transcatheter aortic valve placed so that extension into left ventricular outflow tract (LVOT) that may impinge on the mitral implant. 3. Known residual mean gradient \>10 mmHg at the end of the index procedure for implantation of the original surgical valve. 4. Severe right ventricle (RV) dysfunction. 5. Anatomical characteristics that would preclude safe access to the apex (transapical). 6. Severe regurgitation or stenosis of any other valve. 7. Severe lung disease (FEV1 \< 50% predicted) or currently on home oxygen 8. Severe pulmonary hypertension (e.g., PA systolic pressure ≥ 2/3 systemic pressure) 9. Anatomical characteristics that would increase risk of LVOT obstruction (e.g., aortomitral angle, LVOT size, etc.). 10. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before enrollment. 11. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days prior to the index procedure. Implantation of a permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) is not considered an exclusion. 12. Patients with planned concomitant surgical or transcatheter ablation for atrial fibrillation. 13. Leukopenia (white blood count \< 3000 cell/mL), anemia (hemoglobin \< 9 g/dL), thrombocytopenia (blood platelet count \< 50,000 cell/mL), history of bleeding diathesis or coagulopathy, or hypercoagulable states. 14. Untreated clinically significant coronary artery disease requiring revascularization. 15. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days of enrollment. 16. Emergency intervention/surgical procedures within one month (30 days) prior to the procedure. 17. Any planned surgical, percutaneous coronary, or peripheral procedure to be performed within the 30-day follow-up from the procedure. 18. Hypertrophic cardiomyopathy with obstruction (HOCM). 19. Left ventricular ejection fraction (LVEF) \< 30%. 20. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation. 21. Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure. 22. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication. 23. Stroke or transient ischemic attack (TIA) within 90 days of enrollment. 24. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of enrollment. 25. Renal insufficiency (eGFR \< 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy at the time of screening. 26. Active bacterial endocarditis within 6 months (180 days) of the procedure. 27. Patient refuses blood products. 28. Estimated life expectancy \< 24 months. 29. Currently participating in an investigational drug or another device study. Note: Clinical trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. 30. Positive urine or serum pregnancy test in female subjects of childbearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Effectiveness - Composite of All-cause Mortality and Stroke | 1 Year | Non-hierarchical composite endpoint of all-cause mortality and stroke at 1-year post-procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| New York Heart Association (NYHA) Functional Class - Change From Baseline | 30 Days | 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. A decrease in NYHA class (negative value) shows patient improvement at 30 days. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) - Change From Baseline | 30 days | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom, social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. An increase in KCCQ score (positive value) shows patient improvement at 30 days. |
| Mitral Regurgitation - Change From Baseline | 30 days | Echocardiographic assessment of the degree of mitral valve regurgitation None=0, Trace=0.5, Mild or Mild-Moderate=1, Moderate=2, Moderate-Severe=3, and Severe=4. A decrease in MR (negative value) shows patient improvement at 30 days. |
| Pulmonary Artery Systolic Pressure - Change From Baseline | 30 days | Echocardiographic assessment of pulmonary artery systolic pressure A decrease in pulmonary artery systolic pressure (negative value) shows patient improvement at 30 days. |
Countries
Australia, Brazil, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Failing Mitral Transcatheter Valve Patients with a failing bioprosthetic valve in the mitral position demonstrating stenosis and/or insufficiency will be treated with Edwards SAPIEN 3 transcatheter valve. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Failing Mitral Transcatheter Valve |
|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 9.66 |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Other | 7 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants |
| Race/Ethnicity, Customized White | 31 Participants |
| Region of Enrollment Australia | 4 participants |
| Region of Enrollment Brazil | 12 participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 50 |
| other Total, other adverse events | 15 / 50 |
| serious Total, serious adverse events | 21 / 50 |
Outcome results
Primary
Safety and Effectiveness - Composite of All-cause Mortality and Stroke
Non-hierarchical composite endpoint of all-cause mortality and stroke at 1-year post-procedure
Time frame: 1 Year
Population: Valve implant population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Failing Mitral Transcatheter Valve | Safety and Effectiveness - Composite of All-cause Mortality and Stroke | 0 Participants |
Secondary
Kansas City Cardiomyopathy Questionnaire (KCCQ) - Change From Baseline
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom, social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. An increase in KCCQ score (positive value) shows patient improvement at 30 days.
Time frame: 30 days
Population: Valve implant population - 2 subjects did not complete the 30-day visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Failing Mitral Transcatheter Valve | Kansas City Cardiomyopathy Questionnaire (KCCQ) - Change From Baseline | 31.0 score on a scale | Standard Error 26.06 |
Secondary
Mitral Regurgitation - Change From Baseline
Echocardiographic assessment of the degree of mitral valve regurgitation None=0, Trace=0.5, Mild or Mild-Moderate=1, Moderate=2, Moderate-Severe=3, and Severe=4. A decrease in MR (negative value) shows patient improvement at 30 days.
Time frame: 30 days
Population: Valve implant population - 4 subjects did not receive an echocardiogram at 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Failing Mitral Transcatheter Valve | Mitral Regurgitation - Change From Baseline | -1.4 score on a scale | Standard Error 1.48 |
Secondary
New York Heart Association (NYHA) Functional Class - Change From 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. A decrease in NYHA class (negative value) shows patient improvement at 30 days.
Time frame: 30 Days
Population: Valve implant population - 2 subjects did not complete the 30-day visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Failing Mitral Transcatheter Valve | New York Heart Association (NYHA) Functional Class - Change From Baseline | -1.4 score on a scale | Standard Error 0.73 |
Secondary
Pulmonary Artery Systolic Pressure - Change From Baseline
Echocardiographic assessment of pulmonary artery systolic pressure A decrease in pulmonary artery systolic pressure (negative value) shows patient improvement at 30 days.
Time frame: 30 days
Population: Valve implant population - 35 subjects had data at 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Failing Mitral Transcatheter Valve | Pulmonary Artery Systolic Pressure - Change From Baseline | -9.5 mmHg | Standard Error 14.64 |