Semaglutide in Patients Undergoing Transcatether Aortic Valve Replacement

Summary

This is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial evaluating the safety and efficacy of once-weekly semaglutide 2.4 mg in adult patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) who meet current clinical criteria for semaglutide treatment. A total of 826 participants will be randomized 1:1 to receive semaglutide or placebo as an add-on to standard-of-care, starting 3 months before TAVR and continuing for 24 months post-procedure. The primary endpoint is time to first occurrence of a composite of cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke or transient ischemic accident (TIA), and hospitalization for heart failure (HF). The study is event-driven and powered to detect a 20% relative risk reduction in primary outcome events. This trial aims to address the unmet need for medical therapies that improve outcomes in patients with severe AS following TAVR, with potential for direct clinical implementation.

Timeline

Start

2026-04-01

Primary completion

2030-09-01

Completion

2031-04-01

Publications

• Background Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.
• Background Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30.

Drugs

Indications