PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis

Prospective, randomized, controlled, multi-center trial. Patients having an operative mortality < 4% (low operative risk) for surgical aortic valve replacement will be randomized 1:1 to receive either transcatheter heart valve replacement (TAVR) with the Edwards SAPIEN 3 or aortic valve replacement with a commercially available surgical bioprosthetic valve. Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 10 years.

A subset of PARTNER 3 randomized patients will be enrolled in the Actigraphy/Quality of Life. Additional patients will be enrolled in either the Bicuspid Registry, Underrepresented Populations Registry (UPR) or the Alternative Access Registry.

Inclusion criteria

• Severe, calcific aortic stenosis
• New York Heart Association Functional Class ≥ 2 OR exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR asymptomatic with Left Ventricular Ejection Fraction (LVEF) <50%
• Heart team agrees the patient has a risk of operative mortality and has an Society of Thoracic Surgeons (STS) score < 4
• The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Exclusion criteria

• Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm transcatheter heart valve
• Iliofemoral vessel characteristics that would preclude safe passage of the introducer sheath
• Evidence of an acute myocardial infarction ≤ 30 days before randomization
• Aortic valve is unicuspid, bicuspid, or non-calcified
• Severe aortic regurgitation (>3+)
• Severe mitral regurgitation (>3+) ≥ moderate stenosis
• Pre-existing mechanical or bioprosthetic valve in any position
• Complex coronary artery disease:

• Unprotected left main coronary artery
• Syntax score > 32
• Heart Team assessment that optimal revascularization cannot be performed
• 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
• Ventricular dysfunction with LVEF < 30%
• Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
• Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure
• Stroke or transient ischemic attack within 90 days of randomization
• Renal insufficiency and/or renal replacement therapy at the time of screening.
• 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 or cannulation and aortotomy for surgical aortic valve replacement
• Hostile chest or conditions or complications from prior surgery that would preclude safe reoperation
• Patient refuses blood products
• Body mass index > 50 kg/m2
• Estimated life expectancy < 24 months
• Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
• Immobility that would prevent completion of study procedures
• Patient is not a candidate for both arms of the study
• Currently participating in an investigational drug or another device study.