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NOT YET RECRUITING
NCT07666698
PHASE1/PHASE2

A Study of Metformin to Improve Cardiac Function After LVAD Implantation

Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

View on ClinicalTrials.gov

Summary

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.

Official title: Study on the Effect of Metformin in Improving Cardiac Function After Implantation of Left Ventricular Assist Devices

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

108

Start Date

2026-07

Completion Date

2029-09

Last Updated

2026-06-24

Healthy Volunteers

No

Interventions

DRUG

Metformin Hydrochloride

Metformin hydrochloride tablets, 250 mg and 500 mg, administered orally with a dose-escalation schedule over 10 weeks to achieve target dose, followed by a maintenance period from Week 10 to Week 52. Dose adjustments based on tolerability and renal function.

DRUG

Placebo

Matching placebo tablets, identical in appearance to metformin, administered orally following the same dose-escalation and maintenance schedule as the active comparator.

Locations (1)

Dong-Jin Wang

Nanjing, Jiangsu, China