Balloon vs. Self Expanding Transcatheter Valve for Degenerated Bioprosthesis

Study Overview
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Brief Summary
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Transcatheter aortic valve implantation (TAVI) serves a growing spectrum of patients with symptomatic severe aortic stenosis (AS). Approximately 80% of surgical aortic valve replacements is performed using a bioprosthesis1. Durability of surgical bioprostheses varies based on the patient's age at the moment of implantation, type and size etc2. TAVI has become the preferred treatment for degenerated aortic bioprostheses in elderly patients3. The median time since index surgical aortic valve replacement (SAVR) and for bioprosthetic valve degeneration is typically 8 - 10 years4-6. TAVI in this setting has proven to have equally favorable results as in native aortic valves7. Balloon expandable8 and self-expanding9 transcatheter heart valves (THV) can be used in a degenerated bioprosthesis and each have specific assets and limitations. TAVI in a failed bioprosthesis can cause coronary obstruction, THV migration, paravalvular leakage and prosthesis patient mismatch. The SAPIEN-3 / Ultra and EVOLUT R/Pro are the 2 most commonly used THV platforms in contemporary clinical practice including treatment of failing surgical aortic bioprostheses. Objective: To compare TAVI with EVOLUT R/Pro vs. SAPIEN-3 / Ultra in terms of device success. Study design: International multi-center randomized study with 1:1 randomization to TAVI with SAPIEN-3 / Ultra or Evolut R/Pro. Study population: 440 patients with a failing surgical aortic bioprosthesis (aortic stenosis with or without aortic regurgitation) and selected for transfemoral TAVI by heart-team consensus. Investigational intervention: Transfemoral TAVI with SAPIEN-3 / Ultra or Evolut R/PRO Main study parameters/endpoints: Primary endpoint is device success at 30 days Defined by Absence of procedural mortality AND Correct positioning of a single prosthetic heart valve into the proper anatomical location AND Intended performance of the prosthetic heart valve (no severe prosthesis- patient mismatch and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/s, AND no moderate or severe prosthetic valve regurgitation). Severe prosthesis patient mismatch is defined by effective orifice area (EOAi) ≤0.65 cm2/m2 Safety endpoint at 1 year defined by the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems.

Official Title
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Balloon Expandable vs. Self Expanding Transcatheter Valve for Degenerated Bioprosthesis. THE BASELINE TRIAL.

Conditions
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Valve Heart Disease

Intervention / Treatment
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* Device: Evolut R/PRO bioprosthesis
* Device: Edwards Sapien S3/Ultra bioprosthesis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years Failing surgical aortic bioprosthesis requiring valve replacement and eligible for transfemoral TAVI with balloon expandable or self-expanding platform per heart team consensus based on multi-modality imaging assessment (including echocardiography and multidetector CT). Written informed consent Exclusion Criteria: Not eligible for Transfemoral TAVI with SAPIEN-3 / Ultra and Evolut R/Pro Multi-valve defects requiring intervention Clinically unstable and/or inotropic/vasopressor /mechanical support. Known mural thrombus in the left ventricle Presence of a mechanical aortic valve History of recent (within 1 month) stroke or TIA

Ages Eligible for Study
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Minimum Age: 65 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evolut R/Pro bioprosthesis<br>Study subjects will receive a self-expanding-valve (either the Evolut R or PRO device) | Device: Evolut R/PRO bioprosthesis<br>* To compare Evolut R/PRO versus Sapien S3/Ultra in failing surgical bioprostheses<br>|
| Active Comparator: Edwards Sapien S3/Ultra bioprosthesis<br>Study subjects will receive a balloon-expanding-valve (either the Edwards Sapien S3 or Ultra) | Device: Edwards Sapien S3/Ultra bioprosthesis<br>* Edwards Sapien S3/Ultra bioprosthesis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success | Device success, definition modified from VARC-2 criteria: Absence of procedural mortality AND Correct positioning of a single prosthetic heart valve into the proper anatomical location AND Intended performance of the prosthetic heart valve (no severe prosthesis- patient mismatch and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/s, AND no moderate or severe prosthetic valve regurgitation). Severe prosthesis patient mismatch is defined by effective orifice area (EOAi) ≤0.65 cm2/m2 | 30 days post transcatheter valve implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems | Safety endpoint | 1 year post transcatheter valve implantation |