Heart Failure Clinical Trials

This study investigates whether metformin, compared with placebo, improves cardiac function in patients after Left Ventricular Assist Device (LVAD) implantation. Metformin is a widely used oral medication for type 2 diabetes, but emerging evidence suggests it may have beneficial effects on cardiac metabolism and function independent of its glucose-lowering effects. This is a prospective, multicenter, randomized, double-blind, placebo-controlled trial. A total of 108patients undergoing LVAD implantation will be enrolled from 5 centers in China. Eligible participants will be randomly assigned in a 1:1 ratio to receive either metformin or placebo for 12 months. The primary outcome is the incidence of Full Responder at 12 months post-implantation. A Full Responder is defined as meeting all of the following four criteria: (1) left ventricular ejection fraction (LVEF) ≥40% and left ventricular end-diastolic diameter (LVEDD) ≤6.0 cm (Utah-Inova Responder criteria); (2) soluble ST2 (sST2) ≤100 ng/mL at both 6 months and 12 months post-implantation; (3) absolute value of left ventricular global longitudinal strain (GLS) ≥12% at 12 months post-implantation. Secondary outcomes include clinical events, cardiac function status, blood biomarker results, global functional status and quality of life, medication safety, and exploratory measures. Clinical events assessed up to 24 months post-implantation include: heart failure rehospitalization rate, all-cause mortality, LVAD explantation rate, cardiovascular mortality, major bleeding, cardiac structural damage, thromboembolic events, systemic inflammatory dissemination, sepsis, and other serious adverse events. Cardiac function status is evaluated by echocardiographic parameters (LVEF, LVEDD, GLS) and hemodynamic measures. Blood biomarkers include sST2, NT-proBNP, cardiac troponin, and inflammatory cytokines. Global functional status and quality of life are measured using the 6-minute walk test (6MWT), peak oxygen consumption (VO₂max), and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Safety outcomes include the incidence and severity of adverse events, serious adverse events, and adverse events of special interest. Exploratory outcomes include pre-implantation right ventricular myocardial biopsy (obtained only when clinically indicated for temporary pacemaker lead placement) to assess insulin receptor substrate (IRS)/Akt phosphorylation, G6PD activity, NADPH/NADP⁺ ratio, and oxidative stress markers (malondialdehyde, 4-hydroxynonenal). The study aims to provide evidence on whether adjunctive metformin therapy can improve post-LVAD cardiac outcomes and reduce adverse clinical events.