EARLY TAVR: Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis

Study Overview
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Brief Summary
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This study will evaluate the safety and effectiveness of the Edwards SAPIEN 3/SAPIEN 3 Ultra Transcatheter Heart Valve (THV) compared with clinical surveillance (CS) in asymptomatic patients with severe, calcific aortic stenosis.

Detailed Description
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This is a prospective, randomized, controlled, multicenter study. Patients will be randomized to receive either transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 / SAPIEN 3 Ultra THV or clinical surveillance. Patients will be stratified by whether they are able to perform a treadmill stress test. Patients who have a positive stress test will be followed in a registry to collect data on subsequent treatment and mortality, as applicable.

Official Title
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Evaluation of Transcatheter Aortic Valve Replacement Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis

Conditions
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Heart Diseases, Aortic Stenosis, Severe

Intervention / Treatment
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* Device: Edwards SAPIEN 3 / SAPIEN 3 Ultra THV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 65 years of age or older Severe aortic stenosis Patient is asymptomatic LV ejection fraction ≥ 50% Society of Thoracic Surgeons (STS) risk score ≤ 10 The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent. Exclusion Criteria: Patient is symptomatic Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication. Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath. Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post TAVR Evidence of an acute myocardial infarction ≤ 30 days before randomization Aortic valve is unicuspid, bicuspid with unfavorable features for TAVR, or is non-calcified Severe aortic regurgitation (>3+) Severe mitral regurgitation (>3+) or ≥ moderate mitral stenosis Pre-existing mechanical or bioprosthetic valve in any position Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy, or hypercoagulable states Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization Hypertrophic cardiomyopathy with obstruction Cardiac imaging evidence of intracardiac mass, thrombus or vegetation Inability to tolerate or condition precluding treatment with anti-thrombotic therapy Stroke or transient ischemic attack within 90 days of randomization Renal insufficiency and/or renal replacement therapy Active bacterial endocarditis within 180 days of randomization Severe lung disease or currently on home oxygen Severe pulmonary hypertension History of cirrhosis or any active liver disease Significant frailty as determined by the Heart Team Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system Patient refuses blood products BMI >50 kg/m2 Estimated life expectancy <24 months Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication Currently participating in an investigational drug or another device study. Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAVR<br>Transcatheter aortic valve replacement (TAVR) | Device: Edwards SAPIEN 3 / SAPIEN 3 Ultra THV<br>* Patients will receive the SAPIEN 3 / SAPIEN 3 Ultra THV.<br>* Other names: SAPIEN 3, SAPIEN 3 Ultra;|
| No Intervention: CS<br>Clinical surveillance (CS) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death, all stroke, and unplanned cardiovascular hospitalization | The number of patients that have any of these conditions | When all patients have reached 2-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of 1) alive, 2) Kansas City Cardiomyopathy Questionnaire (KCCQ) score ≥75 and 3) KCCQ decrease ≤10 points | The number of patients that meet all of these criteria | 2 years | 
| Left Ventricular Health | Echocardiographic measurements that will assess the health of the left ventricle | 2 years | 
| Change in Left Ventricular Ejection Fraction (LVEF) | The average change in LVEF from baseline | 2 years | 
| New onset atrial fibrillation | The number of patients that develop this condition | When all patients have reached 2-year follow-up | 
| Death or disabling stroke | The number of patients that have any of these conditions | When all patients have reached 2-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve, Asymptomatic, Transcatheter aortic valve replacement