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

Study Overview
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Brief Summary
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To establish the safety and effectiveness of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in patients with severe, calcific aortic stenosis who are at low operative risk for standard aortic valve replacement.

Detailed Description
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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.

Official Title
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A Prospective, Randomized, Controlled, Multi-Center Study to Establish the Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients Who Have Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Procedure: SAVR
* Device: SAPIEN 3 THV


Participation Criteria
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Eligibility Criteria
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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.
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 |
| --- | --- |
| Active Comparator: Surgical aortic valve replacement (SAVR)<br> | Procedure: SAVR<br>* SAVR with a commercially available bioprosthetic valve.<br>|
| Experimental: Transcatheter aortic valve replacement (TAVR)<br> | Device: SAPIEN 3 THV<br>* TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve and Edwards Commander Delivery System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality, All Stroke, and Rehospitalization (Valve-related or Procedure-related and Including Heart Failure) | Number of patients that had any of these events | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New Onset Atrial Fibrillation | Number of patients with this event | 30 days | 
| Length of Index Hospitalization | Number of days from index procedure to discharge | Discharge (expected average of 7 days) | 
| Death, Kansas City Cardiomyopathy Questionnaire (KCCQ) Score < 45 or KCCQ Score Decrease ≥ 10 Points | Number of patients that had any of these events | 30 days | 
| Death or Stroke | Number of patients that died or had a stroke | 30 days | 
| All Stroke | Number of patients that had a stroke | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SAPIEN 3, cardiovascular disease, heart disease, aortic stenosis, Surgical aortic valve replacement (SAVR), Transcatheter aortic valve replacement (TAVR)