Symptomatic Severe Aortic Stenosis
Conditions
Keywords
SAPIEN XT, Transfemoral, Transapical, Transaortic, NovaFlex, TAVI, Aortic Stenosis, THV, Aortic Valve, Transcatheter Heart Valve, TAVR
Brief summary
The purpose of this trial is to determine the safety and effectiveness of the Edwards SAPIEN XT transcatheter heart valve and delivery systems which are intended for use in patients with symptomatic, calcific, severe aortic stenosis.
Detailed description
The PIIA cohort is a prospective multi-center trial undergoing aortic valve replacement for severe aortic stenosis. Patients randomized to the treatment arm will receive an Edwards SAPIEN XT THV with either transfemoral, transapical or transaortic delivery access. Patients in the control arm will receive a surgical bioprosthetic heart valve via aortic valve replacement surgery. To assure that patients with an STS score ≥ 4% have been selected.
Interventions
Operable Group with SAPIEN XT
DEVICESAVR Implantation
Control Group
Sponsors
Edwards Lifesciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient \>40 mmHg or jet velocity greater than 4.0 m/s and an initial aortic valve area (AVA) of ≤0.8 cm2 or indexed EOA \< 0.5 cm2/m2 Qualifying echo must be within 60 days of the date of the procedure. 2. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater. 3. The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient. 4. The study patient or the study patient'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 Institutional Review Board (IRB) of the respective clinical site. 5. The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up. 6. Study patient agrees to undergo surgical aortic valve replacement (SAVR) - if randomized to control treatment.
Exclusion criteria
1. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment \[defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)\]. 2. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified. 3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation \>3+). 4. Preexisting mechanical or bioprosthetic valve in any position (except NR3). 5. 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). Implantation of a permanent pacemaker or ICD (S3 Cohort only) is not excluded. 6. Heart team assessment of inoperability (including examining cardiac surgeon).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Death or Disabling Stroke to Two Years | 2 Years | All-cause Death or Disabling Stroke (Edwards SAPIEN XT THV vs SAVR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6MWT Change From Baseline | Baseline and 2 years | Six Minute Walk Test change from baseline to 2 years |
| Adjusted Days Alive and Out of Hospital (DAOH) to Two Years | 2 years | The number of days the patients are alive and out of the hospital. |
| Total Aortic Regurgitation (AR) at 2 Years | 2 years | 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 two year was analyzed in the valve implant population. |
| NYHA Classification at 2 Years | 2 years | 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. |
| Effective Orifice Area (EOA) | 2 years | — |
Countries
Canada, United States
Participant flow
Recruitment details
Between December 23, 2011 to November 6, 2013 2,032 patients were enrolled into the PARTNER II A SAPIEN XT vs SAVR Intermediate Risk Trial at 57 sites in the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| PIIA: SAPIEN XT Edwards SAPIEN XT Transcatheter Heart Valve (THV) | 1,011 |
| Control: SAVR Surgical Aortic Valve Replacement (SAVR); Control for PIIA: SAPIEN XT | 1,021 |
| Total | 2,032 |
Baseline characteristics
| Characteristic | Control: SAVR | Total | PIIA: SAPIEN XT |
|---|---|---|---|
| Age, Continuous | 81.7 years STANDARD_DEVIATION 6.71 | 81.6 years STANDARD_DEVIATION 6.7 | 81.5 years STANDARD_DEVIATION 6.7 |
| NYHA Classification NYHA I/II | 244 participants | 473 participants | 229 participants |
| NYHA Classification NYHA III/VI | 776 participants | 1558 participants | 782 participants |
| Sex: Female, Male Female | 461 Participants | 924 Participants | 463 Participants |
| Sex: Female, Male Male | 560 Participants | 1108 Participants | 548 Participants |
| STS Score | 5.8 % risk of mortality or morbidity STANDARD_DEVIATION 1.87 | 5.8 % risk of mortality or morbidity STANDARD_DEVIATION 1.98 | 5.8 % risk of mortality or morbidity STANDARD_DEVIATION 2.08 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 166 / 1,011 | 170 / 1,021 |
| other Total, other adverse events | 838 / 974 | 864 / 936 |
| serious Total, serious adverse events | 666 / 974 | 672 / 936 |
Outcome results
Primary
All-cause Death or Disabling Stroke to Two Years
All-cause Death or Disabling Stroke (Edwards SAPIEN XT THV vs SAVR)
Time frame: 2 Years
Population: Participants include all patients who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PIIA: SAPIEN XT | All-cause Death or Disabling Stroke to Two Years | 192 Participants |
| Control: SAVR | All-cause Death or Disabling Stroke to Two Years | 202 Participants |
Secondary
6MWT Change From Baseline
Six Minute Walk Test change from baseline to 2 years
Time frame: Baseline and 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PIIA: SAPIEN XT | 6MWT Change From Baseline | 14.5 meters | Standard Deviation 128.7 |
| Control: SAVR | 6MWT Change From Baseline | NA meters | — |
Secondary
Adjusted Days Alive and Out of Hospital (DAOH) to Two Years
The number of days the patients are alive and out of the hospital.
Time frame: 2 years
Population: Intent to Treat Population: All randomized patients with the exception of Total Aortic Regurgitation and Effective Orifice Area which was analyzed with the Valve Implant Population: All randomized patients receiving the valve.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PIIA: SAPIEN XT | Adjusted Days Alive and Out of Hospital (DAOH) to Two Years | 629.4 days | Standard Deviation 208.54 |
| Control: SAVR | Adjusted Days Alive and Out of Hospital (DAOH) to Two Years | 597.8 days | Standard Deviation 236.8 |
Secondary
Effective Orifice Area (EOA)
Time frame: 2 years
Population: Effective Orifice Area is listed for only the patients who had echo available at the follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PIIA: SAPIEN XT | Effective Orifice Area (EOA) | 1.5 cm^2 | Standard Deviation 0.4 |
| Control: SAVR | Effective Orifice Area (EOA) | 1.4 cm^2 | Standard Deviation 0.4 |
Secondary
NYHA Classification at 2 Years
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: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PIIA: SAPIEN XT | NYHA Classification at 2 Years | 1.5 units on a scale | Standard Deviation 0.7 |
| Control: SAVR | NYHA Classification at 2 Years | 1.4 units on a scale | Standard Deviation 0.6 |
Secondary
Total Aortic Regurgitation (AR) at 2 Years
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 two year was analyzed in the valve implant population.
Time frame: 2 years
Population: All randomized patients who received the valve were analyzed. Note: Echos were not available for all the patients who made the follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PIIA: SAPIEN XT | Total Aortic Regurgitation (AR) at 2 Years | 1.2 Grade | Standard Deviation 1 |
| Control: SAVR | Total Aortic Regurgitation (AR) at 2 Years | 0.5 Grade | Standard Deviation 0.7 |