TRANscatheter or SurgIcal Aortic Valve ReplacemenT in All-Comers With Severe Aortic Valve Stenosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine that Transcatheter aortic valve replacement (TAVR) with SAPIEN 3 is superior to traditional surgical aortic valve replacement(SAVR) with bio-prosthesis regarding the rate of all-cause mortality at 1 year in patients with symptomatic severe aortic valve stenosis.

Official Title
-----------------
Prospective, Open Label, Multicenter, Dual Arm, Randomized Trial of TRANscatheter or SurgIcal Aortic Valve ReplacemenT in All-Comers With Severe Aortic Valve Stenosis

Conditions
-----------------
Aortic Valve Stenosis

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age must be at least 19 and less than 75 years old Severe aortic valve stenosis with echocardiographically derived criteria: mean gradient > 40mmHg or jet velocity greater than 4.0 m/s AND an initial aortic valve area (AVA) of ≤ 0.8 cm2. Echocardiogram must be within 3 months of the date of the procedure Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA class II or greater. The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site. Exclusion Criteria: Life expectancy <1 year due to medical illness Suspected Malignancy Inoperability evaluated by surgeon Concomitant severe coronary artery disease not amenable for percutaneous coronary intervention Concomitant severe mitral valve or significant aorta disease requiring surgery Active bacterial endocarditis within 6 months of procedure Leukopenia (WBC<3000 cell/mL), acute anemia (Hgb<8g/dL), thrombocytopenia (platelet < 50000 cell/mL) Intracardiac thrombus A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure. Native aortic annulus size < 18 mm or > 25 mm as measured by echocardiogram. Expectation that patient will not improve despite treatment of aortic stenosis Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

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

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

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 with SAPIEN 3 | Device: SAPIEN 3<br> <br> |
| Active Comparator: SAVR<br>Surgical aortic valve replacement | Procedure: SAVR<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event rate of all-cause mortality |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event rate of cardiovascular mortality |  | 30 days or hospital discharge, whichever is longer | 
| event rate of cardiovascular mortality |  | 31 days to the 1 year | 
| event rate of myocardial Infarction |  | 30 days or hospital discharge, whichever is longer | 
| event rate of myocardial Infarction |  | 31 days to the 1 year | 
| event rate of all Stroke and transient ischemic attack |  | 30 days or hospital discharge, whichever is longer | 
| event rate of all Stroke and transient ischemic attack |  | 31 days to the 1 year | 
| event rate of bleeding |  | 30 days or hospital discharge, whichever is longer | 
| event rate of bleeding |  | 31 days to the 1 year | 
| event rate of vascular access site and access-related complication |  | 30 days or hospital discharge, whichever is longer | 
| event rate of vascular access site and access-related complication |  | 31 days to the 1 year | 
| event rate of acute kidney injury |  | 30 days or hospital discharge, whichever is longer | 
| event rate of acute kidney injury |  | 31 days to the 1 year | 
| event rate of permanent pacemaker insertion |  | 30 days or hospital discharge, whichever is longer | 
| event rate of permanent pacemaker insertion |  | 31 days to the 1 year | 
| event rate of other TAVR-related complication | Conversion to open surgery Coronary obstruction Mitral valve apparatus damage or dysfunction Cardiac tamponade Endocarditis Valve thrombosis Valve malpositioning TAV-in-TAV deployment | 30 days or hospital discharge, whichever is longer | 
| event rate of other TAVR-related complication | Conversion to open surgery Coronary obstruction Mitral valve apparatus damage or dysfunction Cardiac tamponade Endocarditis Valve thrombosis Valve malpositioning TAV-in-TAV deployment | 31 days to the 1 year | 
| event rate of prosthetic valve dysfunction | Prosthetic aortic valve stenosis Prosthesis-patient mismatch Prosthetic aortic valve regurgitation | 30 days or hospital discharge, whichever is longer | 
| event rate of prosthetic valve dysfunction | Prosthetic aortic valve stenosis Prosthesis-patient mismatch Prosthetic aortic valve regurgitation | 31 days to the 1 year | 
| event rate of composite event for device success, early safety, clinical efficacy | Number of cases with following events ; A. Device success or B. Early safety (At 30 days): All-cause mortality, all stroke, life threatening bleeding, acute kidney injury, coronary obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure. or C. Clinical efficacy (After 30 days): All-cause mortality, all stroke, requiring hospitalization for valve-related symptoms or worsening congestive heart failure, NYHA class III or IV, valve related dysfunction. | 30 days or hospital discharge, whichever is longer | 
| event rate of composite event for device success, early safety, clinical efficacy | Number of cases with following events ; A. Device success or B. Early safety (At 30 days): All-cause mortality, all stroke, life threatening bleeding, acute kidney injury, coronary obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure. or C. Clinical efficacy (After 30 days): All-cause mortality, all stroke, requiring hospitalization for valve-related symptoms or worsening congestive heart failure, NYHA class III or IV, valve related dysfunction. | 31 days to the 1 year | 
| event rate of structural valve deterioration |  | 30 days or hospital discharge, whichever is longer | 
| event rate of structural valve deterioration |  | 31 days to the 1 year | 
| NYHA (New York Heart Association Functional Classification) |  | 30days and 1 year | 
| Valve area | Aortic valve area (AVA) measured by 2D-transthoracic echocardiography using the continuity equation. | 30days and 1 year | 
| event rate of free from atrial fibrillation |  | 30days and 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Transcatheter aortic valve replacement, TAVR, TAVI, SAVR