Efficacy and Safety of Evogliptin in Mild to Moderate Calcific Aortic Valve Stenosis: The EVOID-AS Trial Rationale and Study Design

The only treatment of severe aortic stenosis (AS) is aortic valve replacement. No medical therapy has been proven effective for preventing or delaying AS progression despite several clinical trials. The EVOID-AS trial is designed to evaluate the efficacy of evogliptin, a dipeptidyl peptidase 4 inhibitor, at retarding the progression of aortic valve calcification and AS hemodynamic severity in patients with mild to moderate AS. In this trial, 580 patients with mild or moderate native calcific AS at 40+ clinical sites across the United States and Canada will be randomized in a 1:1 allocation to receive either evogliptin 10 mg or placebo once daily orally for 2 years. Clinical follow-up visits are scheduled at 3-month intervals; transthoracic echocardiography, aortic valve computed tomography calcium score, and laboratory testing are obtained at baseline, 1-year, and 2-year study visits. The primary end point is change in aortic valve calcification as measured by cardiac computed tomography at 2 years of therapy. Secondary end points are progression of AS hemodynamic severity by echocardiography during 2 years of therapy and time to aortic valve intervention. Secondary safety end points include incidence and severity of treatment-emergent or serious adverse events. Enrollment began in June 2022, and the study is expected to be completed in 2028. EVOID-AS is a double-blind, placebo-controlled, randomized medical trial to modify the progression of calcific AS. This trial will contribute to the critical unmet clinical need of identifying an effective medical therapy to prevent or to delay the progression of AS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05143177.