A Prospective, Randomized, Controlled Trial to Assess the Management of Moderate Aortic Stenosis by Clinical Surveillance or Transcatheter Aortic Valve Replacement

Completed

Conditions: calcific aortic stenosis / narrowing of the heart valve
moderate
10046973

Registration Number: NL-OMON52182

Lead Sponsor: Edwards Lifesciences LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 40

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