To establish the safety and effectiveness of the Edwards SAPIEN 3/ SAPIEN 3 Ultra Transcatheter Heart Valve (THV) in subjects with moderate, calcific aortic stenosis (AS)
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Effectiveness Endpoint: Non-hierarchical composite of the following at 2
years:
death, and heart failure hospitalization or event at 2 years
Safety Endpoint: Non-hierarchical composite of death, stroke, life threatening
or fatal bleeding, acute kidney injury stage 4, hospitalization due to device-
or procedure-related complication, and valve dysfunction requiring
reintervention at 30 days
Secondary outcome
The following will be assessed at 2 years:
• Death, stroke, or unplanned cardiovascular hospitalization
• Death, unplanned cardiovascular hospitalization, decrease of >= 10 points in
Kansas City Cardiomyopathy Questionnaire (KCCQ)
• Unplanned cardiovascular hospitalization
• Left ventricle (LV) mass index
• Stroke volume index
• Diastolic dysfunction >= Grade 2
• N-Terminal Pro-Brain Natriuretic Peptide (NT-ProBNP)
• KCCQ
• Reduction in LVEF >= 5% from baseline AND < 60%
• New onset atrial fibrillation
Background summary
There is no Class 1 indication for treatment of patients with moderate AS.
Current guidelines recommend medical management of risk factors and clinical
surveillance with echocardiographic follow-up every 1-2 years unless the
patient is undergoing cardiac surgery for other indications (Class 2b
indication).
Based on current evidence, patients presenting with moderate AS with specific
characteristics making them more vulnerable or at higher risk for poor outcomes
may benefit from an early intervention before progressing to severe AS and
before accumulating irreversible cardiac damage related to sustained and
prolonged pressure overload. Given the less invasive nature of TAVR and the
favorable outcomes observed in recent trials comparing SAPIEN 3 to SAVR,65,66 a
randomized trial design assessing superiority of TAVR to CS was selected.
The hypothesis for the primary endpoint will test the composite event rate of
the TAVR arm against the rate of the CS arm at a one-sided significance level
of 0.025.
Study objective
To establish the safety and effectiveness of the Edwards SAPIEN 3/ SAPIEN 3
Ultra Transcatheter Heart Valve (THV) in subjects with moderate, calcific
aortic stenosis (AS)
Study design
Prospective, randomized, controlled, multicenter, adaptive design study.
Subjects will be randomized 1:1 to receive either transcatheter aortic valve
replacement (TAVR) with the SAPIEN 3/SAPIEN 3 Ultra THV or CS and will be
stratified by site, left ventricular ejection fraction (LVEF, < 50% and >= 50%)
and peak velocity (< 3 m/s and >= 3 m/s).
Up to 750 patients are planned to be enrolled at up to 80 participating
investigational centers in Europe and North-America. Patient participation will
last for a minimum of 10 years. Patients in the treatment arm will be assessed
at the following intervals: baseline, post-procedure, hospital discharge,
30days, 6 months, 1 year and annually thereafter through 10 years. Patients in
the control group will be assessed yearly up until 10 years.
Intervention
Patients in the treatment arm will receive a CE marked heartvalve for an
off-label indication.
Study burden and risks
The usual risks of a Aorta Valve Replacement are applicable for the patients in
the treatment arm.
The additional burden for the participating patients will concern the
six-minute walking tests and the questionnaires about their quality of life.
One Edwards Way 1
Irvine CA 92614
US
One Edwards Way 1
Irvine CA 92614
US
Listed location countries
Age
Inclusion criteria
1. 65 years of age or older at time of randomization
2. Moderate AS per one of the following as assessed by the Echo Core Lab:
A: Aortic valve area (AVA) / Aortic valve area index (AVAi):
• AVA 1.0 - 1.5 cm2; OR
• AVA < 1.0 with AVAi > 0.6 cm2/m2 if BMI < 30 kg/m2; OR
• AVA < 1.0 with AVAi > 0.5 cm2/m2 if BMI >= 30 kg/m2, OR
• AVA > 1.5 with AVAi < 0.9 cm2/m2 if BMI < 30 kg/m2; OR
• AVA > 1.5 with AVAi < 0.8 cm2/m2 if BMI >= 30 kg/m2
AND
Peak velocity 3.0 - < 4.0 m/s OR mean gradient 20 - < 40 mmHg
OR
B: Subjects who only meet one of the criteria in 2A on resting echo due to
reduced LVEF (< 50%) are eligible if both criteria are met following dobutamine
stress echo (DSE).
Subjects with moderate-severe discordance following DSE are eligible if
non-contrast CT calcium score is < 1200 AU for women or < 2000 AU for men.
Note: Subjects with mild-moderate discordance following DSE are not eligible.
OR
C: Subjects who only meet one of the criteria in 2A on resting echo with
moderate-severe discordance and normal LVEF (>= 50%) are eligible if
non-contrast CT calcium score is < 1200 AU for women or < 2000 AU for men.
Note: Subjects who only meet one of the criteria in 2A on resting echo with
mild-moderate discordance and normal LVEF are not eligible.
3. Subject meets at least one of the following criteria:
• Valve-related symptoms including New York Heart Association functional class
>= II, dyspnea, angina, dizziness, pre-syncope, or syncope deemed to be related
to AS
• LVEF < 60% as assessed by the Echo Core Lab
• Diastolic dysfunction (>= Grade 2) as assessed by the Echo Core Lab per
American Society of Echocardiography Guidelines (i.e., E/e* > 14, left atrium
volume index > 34 mL/m2, or tricuspid regurgitation velocity < 2.8 m/sec)
• Stroke volume index < 35 mL/m2 as assessed by the Echo Core Lab
• Persistent atrial fibrillation or any episode of paroxysmal atrial
fibrillation within 6 months of randomization
• NT-Pro BNP > 3x normal as assessed by the site
• Elevated calcium score as assessed by Computed Tomography (CT) Core Lab (>
1200 AU for female and > 2000 AU for male) (only applicable for subjects
eligible per 2A or 2B above)
4. The subject or subject*s legal representative has been informed of the
nature of the study, agrees to its provisions, and has provided written
informed consent.
Exclusion criteria
1. Native aortic annulus size unsuitable for the THV based on computed
tomography angiography (CTA) analysis
2. Anatomical characteristics that would preclude safe transfemoral placement
of the introducer sheath or safe passage of the delivery system
3. Aortic valve is unicuspid or non-calcified
4. Bicuspid aortic valve with an aneurysmal ascending aorta > 4.5 cm or severe
raphe/leaflet calcification as assessed by CT Core Lab
5. Pre-existing mechanical or bioprosthetic aortic valve
6. Severe aortic regurgitation (>3+)
7. Prior balloon aortic valvuloplasty (BAV) to treat severe AS
8. LVEF < 20% as assessed by the Echo Core Lab
9. Left ventricular outflow tract (LVOT) calcification that would increase the
risk of annular rupture or significant paravalvular leak (PVL) post- TAVR
10. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation
11. Coronary or aortic valve anatomy that increases the risk of coronary artery
obstruction post-TAVR
12. Myocardial infarction within 30 days of randomization
13. Hypertrophic cardiomyopathy with sub-valvular obstruction
14. Any concomitant valvular disease requiring surgical or transcatheter
intervention.
15. Significant untreated coronary artery disease requiring revascularization
16. Any surgical or transcatheter procedure within 30 days of randomization
17. Active bacterial endocarditis within 180 days of randomization
18. Stroke or transient ischemic attack (TIA) within 90 days of randomization
19. Symptomatic carotid or vertebral artery disease or successful treatment of
carotid stenosis within 30 days of randomization
20. Severe chronic obstructive pulmonary disease (COPD, Forced Ejection Volume
1 [FEV1] < 50% predicted) or currently on home oxygen
21. Hemodynamic or respiratory instability requiring inotropic or mechanical
support within 30 days of randomization
22. Liver disease (cirrhosis of the liver [Child-Pugh class B or C])
23. Renal insufficiency (estimated Glomerular Filtration Rate [eGFR] < 30
mL/min per the Cockcroft-Gault formula) and/or renal replacement therapy
24. Significant frailty as determined by the Heart Team
25. Leukopenia (White blood cells < 3000 cells/uL), anemia (Hemoglobin < 9
g/dL), thrombocytopenia (platelets < 50,000 cells/uL)
26. Inability to tolerate or condition precluding treatment with antithrombotic
therapy (including single antiplatelet therapy)
27. Hypercoagulable state or other condition that increases risk of thrombosis
28. Absolute contraindications or allergy to iodinated contrast that cannot be
adequately treated with pre-medication
29. Subject refuses blood products
30. Body mass index (BMI) > 50 kg/m2
31. Estimated life expectancy < 24 months
32. Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously
diagnosed with COVID-19 with sequelae that could confound endpoint assessments
(as assessed by the Case Review Board)
33. Participating in another drug or device study that has not reached its
primary endpoint
34. Subject considered to be part of a vulnerable population
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04889872 |
| CCMO | NL78819.000.21 |