A Study of Metformin to Improve Cardiac Function After LVAD Implantation

Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study ID
NCT07666698
Phase
PHASE1/PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
Jul 31, 2026
Status verified
May 2026
Primary completion
Jul 31, 2027
Completion
Sep 30, 2029

Study Design

Enrollment
108 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Metformin Group
    Metformin hydrochloride tablets administered orally with a dose-escalation schedule to reduce gastrointestinal adverse effects and risk of lactic acidosis. The titration schedule is as follows: Weeks 1-2: 250 mg once daily (after dinner); Weeks 3-4: 500 mg once daily (after dinner); Weeks 5-6: 750 mg total daily (500 mg after dinner + 250 mg after breakfast); Weeks 7-8: 1000 mg total daily (500 mg after dinner + 500 mg after breakfast) - target dose; Weeks 9-10: 1250 mg total daily (500 mg after dinner + 750 mg after breakfast) - optional target dose. The maintenance period extends from Week 10 to Week 52, during which patients maintain the target dose or maximum tolerated dose (must be ≥750 mg per day). Dose adjustment or temporary withholding may be considered based on tolerability and renal function (eGFR).
  • Placebo Comparator: Placebo Group
    Matching placebo tablets, identical in appearance to metformin, administered orally following the same dose-escalation schedule as the metformin group (based on tablet count), from Week 1 through Week 52.

Primary Outcome Measure

Incidence of Full Responder at 12 Months Post-LVAD Implantation [ Time Frame: 12 months post-LVAD implantation ]

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