Design and rationale of the COMPARE-TAVI 2 trial: An all-comers head-to-head comparison of Evolut FX+ and Sapien 3 Ultra Resilia transcatheter heart valves

The COMPARE-TAVI trial framework was launched for direct comparison of transcatheter aortic valve implantation (TAVI) valves. The COMPARE-TAVI 1 trial, comparing Myval/Myval Octacor versus Sapien 3/Sapien 3 Ultra transcatheter heart valves (THVs), was recently published. Here, we present the design and rationale for the COMPARE-TAVI 2 trial comparing the Evolut FX+ self-expandable THV with the Sapien 3 Ultra Resilia balloon-expandable THV. In the COMPARE-TAVI 2 trial (ClinicalTrials.gov NCT06470022), patients will be randomized 1:1 between the THVs. The trial will test whether the Evolut FX+ self-expandable THV is non-inferior to the Sapien 3 Ultra Resilia balloon-expandable THV in terms of the combined 1-year primary composite endpoint of all-cause mortality, stroke, moderate/severe total aortic regurgitation, or moderate/severe hemodynamic THV deterioration, according to VARC-3 criteria. If non-inferiority is proven, superiority analyses may apply. Based on a power of 80%, alpha level of 0.05, one-sided test, non-inferiority margin of 4.5%, and expected event rate of 12%, the necessary sample size has been estimated to be 1364 patients. Prespecified secondary endpoints, including long-term follow-up for 10 years, will also be investigated. The COMPARE-TAVI 2 will provide important information on the short- and long-term outcomes among patients treated with the Evolut FX+ self-expandable and the Sapien 3 Ultra Resilia balloon-expandable THVs. • Majority of previous studies have indicated more aortic regurgitation with self-expandable compared to balloon-expandable transcatheter heart valves (THVs). • COMPARE-TAVI 2 study question: Is the Evolut FX+ non-inferior to the Sapien 3 Ultra Resilia regarding death, stroke, aortic regurgitation or hemodynamic THV-deterioration? • Patients: All comers for transfemoral aortic valve implantation. • Follow-up: Combined primary endpoint at 1 year and long-term follow-up included in secondary endpoints.