PARTNER 3 Trial - Aortic Valve-in-Valve

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety and effectiveness of the SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve (THV) in patients with a failing aortic bioprosthetic valve.

Detailed Description
-----------------
This is a prospective, single-arm, multicenter study.

Official Title
-----------------
A Prospective, Single-Arm, Multicenter Study to Investigate the Safety and Effectiveness of SAPIEN 3/SAPIEN 3 Ultra Transcatheter Heart Valve Implantation in Patients With a Failing Aortic Bioprosthetic Valve

Conditions
-----------------
Aortic Stenosis, Aortic Stenosis, Severe

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Failing surgical or transcatheter bioprosthetic valve in the aortic position demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency. Bioprosthetic valve with a true internal diameter (True ID) of 18.5 mm to 28.5 mm. NYHA Functional Class ≥ II. Heart Team agrees the patient is low to intermediate risk. Heart Team agrees valve implantation will likely benefit the patient. The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent. Exclusion Criteria: Surgical or transcatheter valve in the mitral position (mitral rings are not an exclusion) Severe regurgitation (> 3+) or stenosis of any other valve Failing valve has moderate or severe paravalvular regurgitation Failing valve is unstable, rocking, or not structurally intact Increased risk of coronary obstruction by prosthetic leaflets of the failing valve. Increased risk of embolization of THV Known bioprosthetic valve with residual mean gradient > 20 mmHg at the end of the index procedure for implantation of the original valve Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath (Transfemoral) Anatomical characteristics that would preclude safe access to the ascending aorta (Transaortic) Anatomical characteristics that would preclude safe access to the apex (Transapical) Evidence of an acute myocardial infarction ≤ 30 days before enrollment Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days prior to the index procedure. Implantation of a permanent pacemaker or implantable cardioverter defibrillator is not considered an exclusion. Patients with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy or hypercoagulable states Untreated clinically significant coronary artery disease requiring revascularization Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days of enrollment Emergency interventional/surgical procedures within 30 days prior to the procedure Any planned surgical, percutaneous coronary, or peripheral procedure to be performed within the 30-day follow-up from the procedure Hypertrophic cardiomyopathy with obstruction 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 Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication Stroke or transient ischemic attack within 90 days of enrollment Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of enrollment Renal insufficiency and/or renal replacement therapy at the time of screening Active bacterial endocarditis within 180 days of the procedure Patient refuses blood products Estimated life expectancy < 24 months Positive urine or serum pregnancy test in female subjects of childbearing potential Currently participating in an investigational drug or another device study
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAVR - Failing surgical or transcatheter valve<br>Patients with a failing surgical or transcatheter bioprosthetic valve will undergo transcatheter aortic valve replacement (TAVR). | Device: Edwards SAPIEN 3/SAPIEN 3 Ultra THV<br>* Edwards SAPIEN 3/SAPIEN 3 Ultra THV system with the associated delivery systems.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Effectiveness - Non-hierarchical composite of all-cause mortality and stroke | Number of patients that died and/or had a stroke | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean gradient | Measures the mean aortic pressure gradient from the measured velocity. Units used are mmHg. | 30 days | 
| Peak gradient | Measures the peak aortic pressure gradient from the measured velocity. Units used are mmHg. | 30 days | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | Change from baseline in KCCQ. The KCCQ is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life. | 30 days | 
| New York Heart Association (NYHA) Classification | Change from baseline in NYHA. NYHA is a functional classification of heart failure based on how much a patient is limited during physical activity. The rating ranges from I - IV, with the lowest (I) as no limitations and the highest (IV) unable to carry on any physical activity without discomfort. | 30 days | 
| Six-Minute Walk Test (6MWT) | Change from baseline in 6MWT. The 6-Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
failing bioprosthetic valve, failing valve, SAPIEN 3 Ultra, SAPIEN 3, PARTNER 3, cardiovascular disease, heart disease, aortic stenosis, SAVR, TAVR, failing surgical valve