Safety and Efficacy Comparison Of Two TAVI Systems in a Prospective Randomized Evaluation II

Study Overview
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Brief Summary
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Current care randomized clinical trial comparing the CE marked Symetis ACURATE neo™ Aortic Bioprosthesis and ACURATE TF™ Transfemoral Delivery System with the CE marked Medtronic CoreValve Evolut R TAVI system (or any future CE-marked CoreValve versions).

Detailed Description
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Transcatheter aortic valve implantation (TAVI) is an established and valuable treatment option for patients with severe symptomatic aortic stenosis and at high surgical risk for aortic valve replacement. The use of TAVI is rapidly expanding worldwide and its indications are widening into intermediate and lower risk populations. However, device comparisons by use of randomized trials are scarce in particular for newer generation transcatheter valves. The Symetis ACURATE neo™, a self-expanding transcatheter valve delivered via transfemoral access, is a second-generation device that gained CE mark approval in June 2014. The SCOPE-II trial will compare the safety and performance of the Symetis ACURATE neo™ with the self-expanding Medtronic Evolut R system, a widely used and well-established transcatheter heart valve, which obtained CE mark in 8NOV2006 and HAS approval on 13JAN2015.

Official Title
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Safety and Efficacy Comparison Of Two TAVI Systems in a Prospective Randomized Evaluation II: A Randomized, Controlled, Non-inferiority Trial Evaluating Safety and Clinical Efficacy of the Symetis ACURATE Neo Compared to the Medtronic Evolut R Bioprosthesis in Transfemoral Transcatheter Aortic Valve Implantation

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Symetis ACURATE neo™ transfemoral TAVI system
* Device: Medtronic CoreValve Evolut R TAVI System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with severe symptomatic aortic stenosis defined by a mean aortic gradient > 40 mmHg or peak jet velocity > 4.0 m/s or an aortic valve area (AVA) < 1cm2 or AVA indexed to body surface area (BSA) of <0.6 cm2/m2 Patient is symptomatic (heart failure with New York Heart Association (NYHA) Functional Class > I, angina or syncope) Patients are considered at high risk for mortality with conventional surgical aortic valve replacement as assessed by a Heart Team consisting of a cardiologist and surgeon or as confirmed by a logistic EuroSCORE I > 20% and / or STS score > 10%. Aortic annulus diameter ranging from 21 to 26mm and perimeter rage from 66 - 81.7mm , based on ECG-gated multi-slice computed tomographic measurements. Findings of TTE, TEE and conventional aortography should be integrated in the anatomic assessment. Arterial aorto-iliac-femoral axis suitable for transfemoral access as assessed by conventional angiography and/or multi-detector computed tomographic angiography (access vessel diameter ≥ 6mm) Patient understands the purpose, the potential risks as well as benefits of the trial and is willing to participate in all parts of the follow-up Patient age 75 years or older Patient has given written consent to participate in the trial Exclusion Criteria: Severely reduced left ventricular (LV) function (ejection fraction <20%) Pre-existing prosthetic heart valve in aortic and/or mitral position Participation in another trial, which would lead to deviations in the preparation or performance of the intervention or the post-implantation management from this protocol Severe coagulation conditions Inability to tolerate anticoagulation therapy Contraindication to contrast media or allergy to nitinol Active infection, including endocarditis Congenital aortic stenosis or unicuspid or bicuspid aortic valve Non-valvular aortic stenosis Hypertrophic obstructive cardiomyopathy New or untreated echocardiographic evidence of intracardiac mass, thrombus, or vegetation Non-calcific acquired aortic stenosis Severe eccentricity of calcification Anatomy not appropriate for transfemoral implant due to size, disease and degree of calcification or tortuosity of the aorta or ilio-femoral arteries Severe mitral regurgitation

Ages Eligible for Study
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Minimum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Symetis ACURATE neo™ transfemoral TAVI system<br>Patient assigned to this group will be implanted with Symetis ACURATE neo™ transfemoral TAVI system. | Device: Symetis ACURATE neo™ transfemoral TAVI system<br>* Symetis ACURATE neo™ transfemoral TAVI system: Support frame made of nitinol, supra-annular processed tri-leaflet porcine pericardial valve and an outer skirt to mitigate paravalvular regurgitation (manufactured by Symetis SA, Ecublens, Switzerland).<br>|
| Medtronic CoreValve Evolut R TAVI System<br>Patient assigned to this group will be implanted with Medtronic CoreValve Evolut R Transcatheter Aortic Valve Implantation (TAVI) System. | Device: Medtronic CoreValve Evolut R TAVI System<br>* Medtronic CoreValve Evolut R Transcatheter Aortic Valve Implantation (TAVI) System (or any future CE-marked Corevalve versions): The support frame is manufactured from nitinol, which has multilevel, self-expanding properties and is radiopaque. The bioprosthesis is manufactured by suturing valve leaflets and a skirt from porcine pericardium into a tri-leaflet configuration (manufactured by Medtronic CoreValve LLC, Santa Ana, USA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause mortality or stroke rates | The primary objective is to compare the composite of all-cause mortality or stroke rates at 1 year (powered for non-inferiority). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New permanent pacemaker rate | The first secondary objective is to compare the new permanent pacemaker rate at 30 days (powered for superiority). | 30 days | 
| All cause mortality at 30 days | All cause mortality | 30 days | 
| Stroke at 30 days | Stroke | 30 days | 
| Valve malpositioning at 30 days | Valve malpositioning | 30 days | 
| Peri-procedural myocardial infarction at 30 days | Peri-procedural myocardial infarction | 30 days | 
| Cardiac Tamponade at 30 days | Cardiac Tamponade | 30 days | 
| Implantation of multiple valves (TAV-in-TAV deployment) at 30 days | Implantation of multiple valves (TAV-in-TAV deployment) | 30 days | 
| Annular rupture/dissection at 30 days | - Annular rupture/dissection | 30 days | 
| Left ventricular perforation at 30 days | - Left ventricular perforation | 30 days | 
| Conversion to open heart surgery at 30 days | - Conversion to open heart surgery | 30 days | 
| Intra-procedural mortality (during index procedure) | - Intra-procedural mortality (during index procedure) | Procedurally | 
| Procedural mortality (up to 72 hours after procedure) | - Procedural mortality (up to 72 hours after procedure) | Procedurally and up to 72 hours post-procedurally | 
| Mortality (cardiac/non-cardiac) at 30 days and 1 year | - Mortality (cardiac/non-cardiac) | 30 days and 1 year | 
| All stroke (disabling/non disabling) at 30 days and 1 year | - All stroke (disabling/non disabling) | 30 days and 1 year | 
| Composite of all-cause mortality or disabling stroke at 30 days and 1 year | - Composite of all-cause mortality or disabling stroke | 30 days and 1 year | 
| Hospitalization for valve-related symptoms or worsened congestive heart at 30 days and 1 year | - Hospitalization for valve-related symptoms or worsened congestive heart failure | 30 days and 1 year | 
| Life-threatening/major bleeding at 30 days and 1 year | - Life-threatening/major bleeding (BARC 3b or more) | 30 days and 1 year | 
| Myocardial infarction at 30 days and 1 year | - Myocardial infarction | 30 days and 1 year | 
| Valve related dysfunction requiring repeat procedure at 30 days and 1 year | - Valve related dysfunction requiring repeat procedure (BAV, TAVI or SAVR) | 30 days and 1 year | 
| Endocarditis at 30 days and 1 year | - Endocarditis | 30 days and 1 year | 
| Valve thrombosis at 30 days and 1 year | - Valve thrombosis | 30 days and 1 year | 
| New AV-conduction disturbances at 30 days and 1 year | - New AV-conduction disturbances (LBBB only) | 30 days and 1 year | 
| New pacemaker implantation at 1 year | - New pacemaker implantation at 1 year | 1 year | 
| Any arrhythmia resulting in hemodynamic instability or requiring therapy at 30 days and 1 year | Any arrhythmia resulting in hemodynamic instability or requiring therapy | 30 days and 1 year | 
| VARC-2 combined endpoints at 30 days | Composite of device success, early safety, clinical efficacy and time-related valve safety | 30 days | 
| Time-related valve safety at 1 year | Time-related valve safety | 1 year | 
| Echocardiographic endpoint (1) | - Structural valve deterioration | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (2) | - Prosthetic aortic valve stenosis | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (3) | - Patient prosthesis mismatch | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (4) | - Aortic regurgitation (grading), proportion of more than mild regurgitation | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (5) | - Intended valve performance: No prosthesis mismatch, mean aortic valve gradient <20 mmHg or peak velocity <3 m/s, without moderate or severe prosthetic valve aortic regurgitation. | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (6) | - Systolic LV ejection fraction | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (7) | - LV diastolic function | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (8) | - Left atrial volume | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (9) | - Right ventricular (RV) dimension and function | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (10) | - Right atrial (RA) area | Post-procedurally [day 1 to 7], at 30 days, 1 year | 
| Echocardiographic endpoint (11) | - RV/RA-ratio and estimated systolic pulmonary arterial pressure | Post-procedurally [day 1 to 7], at 30 days, 1 year |