Calcific Aortic Stenosis, Severe, Symptomatic
Conditions
Keywords
SAPIEN, TAVR, THV, Aortic Stenosis, Heart Valve Disease, Aortic Valve, Retroflex, SAPIEN XT
Brief summary
The purpose of this study is to determine the safety and effectiveness of the SAPIEN XT™ THV with the associated delivery system for inoperable patients with severe symptomatic native aortic stenosis.
Detailed description
Cohort B was a 1:1 randomized, controlled study independently powered to compare transcatheter heart valve therapy with the first generation (SAPIEN™ THV) system to transcatheter heart valve therapy with the second generation (SAPIEN XT THV) system in patients who could not undergo surgery (inoperable). Patients in the control arm of Cohort B received an Edwards SAPIEN THV with the associated delivery system while patients in the treatment arm of Cohort B received an Edwards SAPIEN XT THV with the associated delivery system.
Interventions
Inoperable operable patients requiring the transcatheter aortic heart valve replacement
DEVICETAVR Implantation with SAPIEN
Inoperable operable patients requiring the transcatheter aortic heart valve replacement
Sponsors
American College of Cardiology
Edwards Lifesciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient was symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater. 2. The probability of death or serious, irreversible morbidity is greater than or equal to 50%. 3. The heart team agreed (and verified in the case review process) that valve implantation would likely benefit the patient. 4. The study patient or the study patient's legal representative was informed of the nature of the study, agreed to its provisions and had provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site. 5. The study patient agreed to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which was conducted as a phone follow-up.
Exclusion criteria
1. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified. 2. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma \[especially if thick (\> 5 mm), protruding or ulcerated\] or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe unfolding and tortuosity of the thoracic aorta. (Transfemoral) 3. Currently participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. 4. It is known that the patient is currently enrolled in the PARTNER I Trial or was withdrawn from the PARTNER I Trial prior to endpoint analysis. 5. Active bacterial endocarditis within 6 months (180 days) of procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-Cause Mortality and/or Major Stroke and/or Rehospitalization | 1 Year | All-Cause Mortality and/or Major Stroke and/or Rehospitalization at 1 Year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NYHA Classification - Change From Baseline | Baseline and 1 Year | New York Heart Association (NYHA), 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 as no limitations and the highest unable to carry on any physical activity without discomfort. |
| Total Aortic Regurgitation - Change From Baseline | 1 Year | Total aortic regurgitation was assessed by the core lab as 'Grade 0' = None, 'Grade 1+' = Trace, 'Grade 2+' = Mild, 'Grade 3+' = Moderate, and 'Grade 4+' = Severe. Total regurgitation at one year was analyzed in the valve implant population. |
| Effective Orifice Area - Change From Baseline | 1 Year | — |
Countries
United States
Participant flow
Recruitment details
Subjects were screened and enrolled at 53 sites in the US and Canada
Participants by arm
| Arm | Count |
|---|---|
| TAVR - SAPIEN XT TAVR (transaortic valve replacement) with SAPIEN XT
TAVR Implantation with SAPIEN XT: Inoperable operable patients requiring the transcatheter aortic heart valve replacement | 284 |
| TAVR - SAPIEN TAVR (transaortic valve replacement) with SAPIEN is the control arm
TAVR Implantation with SAPIEN: Inoperable operable patients requiring the transcatheter aortic heart valve replacement | 276 |
| Total | 560 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 61 | 65 |
| Overall Study | Withdrawal by Subject | 3 | 11 |
Baseline characteristics
| Characteristic | TAVR - SAPIEN | Total | TAVR - SAPIEN XT |
|---|---|---|---|
| Age, Continuous | 84.6 Years STANDARD_DEVIATION 8.61 | 84.3 Years STANDARD_DEVIATION 8.63 | 84.0 Years STANDARD_DEVIATION 8.65 |
| Coronary Artery Disease | 186 Participants | 372 Participants | 186 Participants |
| Frailty | 166 Participants | 334 Participants | 168 Participants |
| NYHA Class III/IV | 265 Participants | 540 Participants | 275 Participants |
| Sex: Female, Male Female | 134 Participants | 277 Participants | 143 Participants |
| Sex: Female, Male Male | 142 Participants | 283 Participants | 141 Participants |
| STS Score | 11.0 units on a scale STANDARD_DEVIATION 5.71 | 10.6 units on a scale STANDARD_DEVIATION 5.55 | 10.3 units on a scale STANDARD_DEVIATION 5.38 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 282 | 12 / 271 |
| other Total, other adverse events | 211 / 280 | 195 / 263 |
| serious Total, serious adverse events | 196 / 280 | 180 / 263 |
Outcome results
Primary
Number of Participants With All-Cause Mortality and/or Major Stroke and/or Rehospitalization
All-Cause Mortality and/or Major Stroke and/or Rehospitalization at 1 Year
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAVR - SAPIEN XT | Number of Participants With All-Cause Mortality and/or Major Stroke and/or Rehospitalization | 105 participants |
| TAVR - SAPIEN | Number of Participants With All-Cause Mortality and/or Major Stroke and/or Rehospitalization | 102 participants |
Secondary
Effective Orifice Area - Change From Baseline
Time frame: 1 Year
Population: Valve Implant Population; Please note that echo data was not available for all patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAVR - SAPIEN XT | Effective Orifice Area - Change From Baseline | 0.9 cm^2 | Standard Deviation 0.41 |
| TAVR - SAPIEN | Effective Orifice Area - Change From Baseline | 0.9 cm^2 | Standard Deviation 0.38 |
Secondary
NYHA Classification - Change From Baseline
New York Heart Association (NYHA), 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 as no limitations and the highest unable to carry on any physical activity without discomfort.
Time frame: Baseline and 1 Year
Population: Please note that all the patients were not available for a NYHA functional assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAVR - SAPIEN XT | NYHA Classification - Change From Baseline | -1.8 Units on a scale | Standard Deviation 0.92 |
| TAVR - SAPIEN | NYHA Classification - Change From Baseline | -1.7 Units on a scale | Standard Deviation 0.91 |
Secondary
Total Aortic Regurgitation - Change From Baseline
Total aortic regurgitation was assessed by the core lab as 'Grade 0' = None, 'Grade 1+' = Trace, 'Grade 2+' = Mild, 'Grade 3+' = Moderate, and 'Grade 4+' = Severe. Total regurgitation at one year was analyzed in the valve implant population.
Time frame: 1 Year
Population: Please note that all the valve-implant population do not have echo data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAVR - SAPIEN XT | Total Aortic Regurgitation - Change From Baseline | 0.2 Grade | Standard Deviation 1.38 |
| TAVR - SAPIEN | Total Aortic Regurgitation - Change From Baseline | 0.1 Grade | Standard Deviation 1.23 |