Stroke Clinical Trials

Objective: To compare valve-in-valve TAVI with balloon-expandable SAPIEN/MYVAL THV series versus the self-expanding EVOLUT THV series. The primary analysis evaluates device success at 30 days in the primary cohort. Continued enrollment will additionally support a secondary comparison of the safety and efficacy of the SAPIEN and MYVAL THV series. Study design: International multicenter randomized study with 1:1 randomization to TAVI with the EVOLUT THV series or the SAPIEN/MYVAL THV series. Study population: The primary cohort comprises 440 patients with a failing surgical aortic bioprosthesis (aortic stenosis with or without aortic regurgitation) selected for transfemoral TAVI by heart-team consensus. Enrollment of the primary cohort has been completed. The continued-enrollment cohort comprises 160 additional patients and will increase the total study population to 600 patients, with a target distribution of 300 patients treated with the EVOLUT THV series, 150 with the SAPIEN THV series, and 150 with the MYVAL THV series. Investigational intervention: Transfemoral valve-in-valve TAVI with a balloon-expandable SAPIEN or MYVAL THV series or a self-expanding EVOLUT THV series. Main study parameters/endpoints: 1. Primary endpoint is device success at 30 days Defined by: * Absence of procedural mortality; AND * Technical success at exit from the procedure room defined as freedom from mortality, successful access, delivery of the device and retrieval of the delivery system, correct positioning of a single prosthetic heart valve into the proper anatomical location, and freedom from surgery or intervention related to the device or to a major vascular or access-related, or cardiac structural complication; 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, Doppler velocity index ≥0.25, and no moderate or severe prosthetic valve regurgitation). Severe prosthesis-patient mismatch is defined as an indexed effective orifice area (EOAi) ≤0.65 cm²/m² (≤0.55 cm²/m² if BMI ≥30 kg/m²). 2. Safety endpoint at 1 year defined by the composite of all-cause death, disabling stroke, rehospitalization for heart failure, or valve-related problems. 3. Secondary objective is comparison of the safety and efficacy of the SAPIEN versus MYVAL THV series, including the incidence of moderate or severe prosthesis-patient mismatch. The continued-enrollment cohort is designed to support this comparison.