Design and rationale of the prospective, randomized, controlled trial to assess the management of moderate aortic stenosis by clinical surveillance or transcatheter aortic valve replacement: The PROGRESS Trial

BACKGROUND: For patients with moderate aortic stenosis (AS), current US guidelines recommend clinical surveillance every 1 to 2 years. However, moderate AS has been associated with increased morbidity and mortality in multiple observational studies, suggesting a possible role for earlier treatment with transcatheter aortic valve replacement (TAVR). To date, no large, randomized trial has examined whether an early intervention with TAVR will improve outcomes among these patients. STUDY DESIGN AND OBJECTIVES: The PROGRESS trial is a prospective, open-label, randomized, controlled, multicenter trial that includes up to 750 patients with moderate AS and at-risk features randomized 1:1 to either clinical surveillance or transfemoral TAVR with the SAPIEN 3/SAPIEN 3 Ultra/SAPIEN 3 Ultra RESILIA transcatheter heart valve (Edwards Lifesciences, Irvine, CA). Patients are stratified by site, left ventricular ejection fraction, and peak jet velocity. The primary effectiveness endpoint is the composite of death or heart failure event with or without hospitalization at 2 years. The primary safety endpoint (evaluated in the TAVR arm only) is a composite of death, stroke, life threatening or fatal bleeding, acute kidney injury stage 4, hospitalization due to device- or procedure-related complications, or valve dysfunction requiring reintervention at 30 days. Patients will be followed annually through 10 years. CONCLUSIONS: The PROGRESS trial is the first large, randomized trial assessing the role of early intervention among patients with moderate AS with at-risk features compared to clinical surveillance. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04889872.