Critical Aortic Stenosis
Conditions
Keywords
Valvular Heart Disease, Critical/Severe Aortic Stenosis, High risk symptomatic patients
Brief summary
The purpose of this study is to determine the safety and effectiveness of the device and delivery systems (transfemoral and transapical) in high risk, symptomatic patients with severe aortic stenosis.
Detailed description
Subjects will undergo a physical exam and screening tests will be performed to determine if they are either A) a patient with a high surgical risk or B) not a candidate for surgery. They will then be randomized (like the flip of a coin) to have the investigational device implanted or to receive the current surgical or medical management available.
Interventions
OTHERmedical management and/or balloon aortic valvuloplasty
Sponsors
Edwards Lifesciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Cohort A 1. Patients must have co-morbidities such that the surgeon and cardiologist Co-PIs concur that the predicted risk of operative mortality is ≥15% and/or a minimum STS score of 10 2. Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient \>40 mmHg or jet velocity greater than 4.0 m/s or an initial aortic valve area of \< 0.8 cm2 3. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater 4. The subject or the subject's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site 5. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits Cohort B All candidates for Cohort B of this study must meet #2, 3, 4, 5 of the above criteria and 6. The subject, after formal consults by a cardiologist and two cardiovascular surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the probability of death or serious, irreversible morbidity should exceed 50%.
Exclusion criteria
1. Evidence of an acute myocardial infarction ≤ 1month before the intended treatment. 2. Aortic valve is a congenital unicuspid or bicuspid valve; or is non-calcified 3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation \>3+). 4. Any therapeutic invasive cardiac procedure performed within 30 days of the index procedure, (or 6 months if the procedure was a drug eluting coronary stent implantation). 5. Pre-existing prosthetic heart valve in any position, prosthetic ring, or severe (greater than 3+) mitral insufficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death | 1 Year | Death from any cause. |
| Composite of Death and Recurrence Hospitalization. | duration of study | Death from any cause or repeat hospitalization after intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Change of NYHA | Baseline to 1 year | NYHA classification change from baseline to 1 year visit. NYHA provides a way of classifying the extent of heart failure. New York Heart Association (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. |
| Number of Participants With Major Adverse Cardiac and Cerebro-vascular Events (MACCE) | 1 year | Number of participants with MACCE definition includes death, myocardial infarction (MI), stroke and renal failure |
| Total Hospital Days From the Index Procedure | 1 year | Total hospital days from the index procedure or randomization into control arm to one year post procedure or randomization. |
| Change in Quality of Life (QOL) From Baseline to 1 Year | Baseline and 1 Year | The QOL questionnaire consisted of: Kansas City Cardiomyopathy (KCCQ), The Medical Outcomes Study Short-Form 12 (SF-12) - physical and metal states. KCCQ scores are on a range of 0-100, in which 100 reflects the best health status and 0 reflects the worst health status. SF-12 questionnaire was used in which 100 reflects the best health status and 0 reflects the worst health status. |
Countries
Canada, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Risk: TAVR Edwards SAPIEN Transcatheter Heart Valve | 348 |
| High Risk: SAVR Surgical Valve Replacement | 349 |
| Inoperable TAVR Edwards SAPIEN Transcatheter Heart Valve | 179 |
| Inoperable: Medical Therapy Medical management and/or balloon aortic valvuloplasty | 179 |
| Total | 1,055 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Alive and censored prior to 1 year | 2 | 0 | 0 | 0 |
| Overall Study | Death | 84 | 89 | 55 | 89 |
| Overall Study | Lost to Follow-up | 1 | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 23 | 0 | 5 |
Baseline characteristics
| Characteristic | High Risk: TAVR | High Risk: SAVR | Inoperable TAVR | Inoperable: Medical Therapy | Total |
|---|---|---|---|---|---|
| Age, Continuous High Risk | 83.61 Years STANDARD_DEVIATION 6.83 | 84.52 Years STANDARD_DEVIATION 6.37 | NA Years | NA Years | 84.11 Years STANDARD_DEVIATION 6.61 |
| Age, Continuous Inoperable | NA Years | NA Years | 83.12 Years STANDARD_DEVIATION 8.6 | 83.18 Years STANDARD_DEVIATION 8.29 | 83.18 Years STANDARD_DEVIATION 8.43 |
| NYHA Class High Risk Class II | 20 Participants | 21 Participants | NA Participants | NA Participants | 41 Participants |
| NYHA Class High Risk Class III or IV | 328 Participants | 328 Participants | NA Participants | NA Participants | 656 Participants |
| NYHA Class Inoperable Class III or IV | NA Participants | NA Participants | 165 Participants | 168 Participants | 333 Participants |
| NYHA Class Operable Class II | NA Participants | NA Participants | 14 Participants | 11 Participants | 25 Participants |
| Quality of Life High Risk KCCQ Overall | 39.6 Score STANDARD_DEVIATION 21.8 | 44.5 Score STANDARD_DEVIATION 21.8 | NA Score | NA Score | 41.88 Score STANDARD_DEVIATION 21.93 |
| Quality of Life High Risk SF-12 Mental | 46.9 Score STANDARD_DEVIATION 11.5 | 47.6 Score STANDARD_DEVIATION 10.7 | NA Score | NA Score | 47.2 Score STANDARD_DEVIATION 11.1 |
| Quality of Life High Risk SF-12 Physical | 29.6 Score STANDARD_DEVIATION 7.6 | 30.9 Score STANDARD_DEVIATION 8.2 | NA Score | NA Score | 30.2 Score STANDARD_DEVIATION 7.9 |
| Quality of Life Inoperable KCCQ Overall | NA Score | NA Score | 36.19 Score STANDARD_DEVIATION 20.52 | 34.44 Score STANDARD_DEVIATION 20.14 | 35.35 Score STANDARD_DEVIATION 20.32 |
| Quality of Life Inoperable SF-12 Mental | NA Score | NA Score | 44.45 Score STANDARD_DEVIATION 12.16 | 45.23 Score STANDARD_DEVIATION 11.03 | 44.84 Score STANDARD_DEVIATION 11.5 |
| Quality of Life Inoperable SF-12 Physical | NA Score | NA Score | 28.23 Score STANDARD_DEVIATION 7.73 | 27.70 Score STANDARD_DEVIATION 6.89 | 28.0 Score STANDARD_DEVIATION 7.23 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized Black/African American | 11 Participants | 8 Participants | 4 Participants | 9 Participants | 32 Participants |
| Race/Ethnicity, Customized Hispanic | 9 Participants | 9 Participants | 5 Participants | 8 Participants | 31 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 324 Participants | 328 Participants | 165 Participants | 162 Participants | 979 Participants |
| Sex: Female, Male Female | 147 Participants | 151 Participants | 97 Participants | 95 Participants | 490 Participants |
| Sex: Female, Male Male | 201 Participants | 198 Participants | 82 Participants | 84 Participants | 565 Participants |
| STS Score High Risk | 11.8 Percentage STANDARD_DEVIATION 3.3 | 11.7 Percentage STANDARD_DEVIATION 3.5 | NA Percentage | NA Percentage | 11.75 Percentage STANDARD_DEVIATION 3.4 |
| STS Score Inoperable | NA Percentage | NA Percentage | 11.2 Percentage STANDARD_DEVIATION 5.8 | 11.9 Percentage STANDARD_DEVIATION 4.8 | 11.51 Percentage STANDARD_DEVIATION 5.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 230 / 348 | 217 / 351 | 140 / 179 | 103 / 179 |
| serious Total, serious adverse events | 228 / 348 | 238 / 351 | 134 / 179 | 151 / 179 |
Outcome results
Primary
Composite of Death and Recurrence Hospitalization.
Death from any cause or repeat hospitalization after intervention.
Time frame: duration of study
Population: Composite of Death and recurrence hospitalization was not a primary outcome for the High Risk groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Risk: TAVR | Composite of Death and Recurrence Hospitalization. | 76 participants |
| High Risk: SAVR | Composite of Death and Recurrence Hospitalization. | 126 participants |
Primary
Death
Death from any cause.
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Risk: TAVR | Death | 84 participants |
| High Risk: SAVR | Death | 89 participants |
| Inoperable: TAVR | Death | 55 participants |
| Inoperable: Medical Therapy | Death | 89 participants |
Secondary
Change in Quality of Life (QOL) From Baseline to 1 Year
The QOL questionnaire consisted of: Kansas City Cardiomyopathy (KCCQ), The Medical Outcomes Study Short-Form 12 (SF-12) - physical and metal states. KCCQ scores are on a range of 0-100, in which 100 reflects the best health status and 0 reflects the worst health status. SF-12 questionnaire was used in which 100 reflects the best health status and 0 reflects the worst health status.
Time frame: Baseline and 1 Year
Population: Note that the number of participants analyzed is different from that in the participant flow as there was some missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Risk: TAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Mental | 52.0 Units on a scale | Standard Deviation 10.1 |
| High Risk: TAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Physical | 36.3 Units on a scale | Standard Deviation 11 |
| High Risk: TAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | KCCQ Overall | 70.0 Units on a scale | Standard Deviation 22.4 |
| High Risk: SAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Physical | 36.9 Units on a scale | Standard Deviation 10.4 |
| High Risk: SAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | KCCQ Overall | 71.1 Units on a scale | Standard Deviation 23 |
| High Risk: SAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Mental | 52.9 Units on a scale | Standard Deviation 9.7 |
| Inoperable: TAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Mental | 53.31 Units on a scale | Standard Deviation 10 |
| Inoperable: TAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | KCCQ Overall | 69.41 Units on a scale | Standard Deviation 25.37 |
| Inoperable: TAVR | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Physical | 34.85 Units on a scale | Standard Deviation 11.13 |
| Inoperable: Medical Therapy | Change in Quality of Life (QOL) From Baseline to 1 Year | KCCQ Overall | 46.98 Units on a scale | Standard Deviation 24.59 |
| Inoperable: Medical Therapy | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Mental | 46.59 Units on a scale | Standard Deviation 11.68 |
| Inoperable: Medical Therapy | Change in Quality of Life (QOL) From Baseline to 1 Year | SF-12 Physical | 29.68 Units on a scale | Standard Deviation 6.47 |
Secondary
Functional Change of NYHA
NYHA classification change from baseline to 1 year visit. NYHA provides a way of classifying the extent of heart failure. New York Heart Association (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.
Time frame: Baseline to 1 year
Population: Note that the number of participants analyzed is different from that in the participant flow as there was some missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High Risk: TAVR | Functional Change of NYHA | 2.50 Units on scale |
| High Risk: SAVR | Functional Change of NYHA | 2.60 Units on scale |
| Inoperable: TAVR | Functional Change of NYHA | 2.88 Units on scale |
| Inoperable: Medical Therapy | Functional Change of NYHA | 3.92 Units on scale |
Secondary
Number of Participants With Major Adverse Cardiac and Cerebro-vascular Events (MACCE)
Number of participants with MACCE definition includes death, myocardial infarction (MI), stroke and renal failure
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Risk: TAVR | Number of Participants With Major Adverse Cardiac and Cerebro-vascular Events (MACCE) | 93 participants |
| High Risk: SAVR | Number of Participants With Major Adverse Cardiac and Cerebro-vascular Events (MACCE) | 97 participants |
| Inoperable: TAVR | Number of Participants With Major Adverse Cardiac and Cerebro-vascular Events (MACCE) | 61 participants |
| Inoperable: Medical Therapy | Number of Participants With Major Adverse Cardiac and Cerebro-vascular Events (MACCE) | 93 participants |
Secondary
Total Hospital Days From the Index Procedure
Total hospital days from the index procedure or randomization into control arm to one year post procedure or randomization.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk: TAVR | Total Hospital Days From the Index Procedure | 17.42 Days | Standard Deviation 19.05 |
| High Risk: SAVR | Total Hospital Days From the Index Procedure | 20.14 Days | Standard Deviation 23.85 |
| Inoperable: TAVR | Total Hospital Days From the Index Procedure | 25.24 Days | Standard Deviation 21.11 |
| Inoperable: Medical Therapy | Total Hospital Days From the Index Procedure | 17.04 Days | Standard Deviation 33.46 |