About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
Adults (≥18 years) undergoing TAVR for severe AS, and
BMI ≥30 kg/m2, or
Dysglycemia (prediabetes or type 2 diabetes) ≥90 days prior to the day of screening with HbA1c of ≤ 10.0% as measured at the screening visit.
Disqualifiers
Treatment with an GLP-1 receptor agonist within the previous 90 days.
Myocardial infarction, stroke, hospitalization for unstable angina or transient ischemic attack within the previous 60 days.
Planned coronary, carotid or peripheral artery revascularization known on the day of screening.
eGFR <25 mL/min/1.73 m² or intermittent hemodialysis or peritoneal dialysis.
Trial design
Parallel
Treatments tested in this trial
Wegovy ®
DrugSemaglutide 2.4 mg subcutaneous once-weekly starting 3 months prior TAVR and continued 24 months post-TAVR. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose as an add-on to standard-of-care. The treatment will continue until the 'end of treatment' visit followed by a 8 weeks follow-up period.
Placebo
DrugMatching placebo subcutaneous once-weekly.
Treatment groups
Trial outcomes
Primary outcomes
CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF
From randomization to first occurrence of a composite endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF.
Secondary outcomes
Incidence rate of each component of the primary outcome.
Change in high sensitivity C-Reactive Protein (hsCRP) (mg/L)
A 5-component composite nephropathy endpoint consisting of: onset of persistent macroalbuminuria, persistent 50% reduction in eGFR compared with baseline (randomization), onset of persistent eGFR < 15 ml/min/1.73m2, initiation of chronic renal replacemen
Change in Lipid Profile (mg/dL)
Locations
Sponsors and contacts
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