Heart FailurePhase 1/2NCT07666698
A Study of Metformin to Improve Cardiac Function After LVAD Implantation
A Phase 1/2 study testing Metformin Hydrochloride in people with Heart Failure and Left Ventricular Assist Device, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 5 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Failure, Left Ventricular Assist Device
- What is being tested?
- Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 5 sitesChina
- Study dates
- 1 Jul 2026to Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years
- Receiving continuous-flow LVADs, such as HeartMate 3, HVAD, Core-Heart 6, Brio-Heart
- Presence of insulin resistance
- HbA1c ≤ 6.5%
Who cannot join
- Diagnosed type 1 diabetes mellitus, or type 2 diabetes mellitus with HbA1c > 6.5% (patients with prior type 2 diabetes who are currently off therapy and have HbA1c ≤ 6.5% may be enrolled; such patients may still have insulin resistance but have achieved glycemic control)
- History of diagnosed diabetic ketoacidosis or hyperosmolar hyperglycemic state
- Currently using any glucose-lowering medications (including insulin, oral hypoglycemic agents, GLP-1 receptor agonists, SGLT2 inhibitors, etc.)
- History of diagnosed polycystic ovary syndrome (PCOS) and currently undergoing treatment
- Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m² (CKD-EPI equation)
- History of acute kidney injury (KDIGO criteria) with incomplete renal recovery
Show all 42Show fewer
- Receiving any form of renal replacement therapy (hemodialysis, peritoneal dialysis)
- Post-kidney transplantation or awaiting kidney transplantation
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3× the upper limit of normal, total bilirubin > 2× upper limit of normal, or Child-Pugh class B or C cirrhosis
- Active viral hepatitis
- History of alcoholic liver disease or drug-induced liver injury currently in the active phase
- Concurrent right ventricular assist device (RVAD) or total artificial heart implantation
- LVAD-related complications requiring surgical intervention within 30 days postoperatively, including but not limited to: pump thrombosis requiring LVAD exchange or thrombolysis, driveline infection requiring debridement or replacement, hemorrhagic complications requiring re-sternotomy, device malfunction requiring urgent intervention
- Acute kidney injury requiring ongoing renal replacement therapy (CRRT) within 30 days postoperatively
- Preoperative severe right heart failure (on echocardiography: right ventricular fractional area change < 35%, or tricuspid annular plane systolic excursion < 14 mm; or right heart catheterization showing central venous pressure > 15 mmHg and cardiac index < 2.0 L/min/m²)
- Preoperative severe pulmonary arterial hypertension (mean pulmonary arterial pressure ≥ 40 mmHg and pulmonary vascular resistance ≥ 4 Wood units)
- Within 30 days postoperatively, occurrence of severe low cardiac output syndrome requiring extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) support
- Significant prosthetic valve dysfunction or severe prosthetic valve infectious endocarditis
- Severe unrepaired valvular disease
- Active systemic infection or sepsis requiring ongoing intravenous antibiotics or antifungal therapy
- Active infectious endocarditis (modified Duke criteria) or high clinical suspicion
- Human immunodeficiency virus (HIV) infection with CD4 count < 200/μL or not on regular antiretroviral therapy
- Active tuberculosis or non-tuberculous mycobacterial infection
- Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection
- Known active inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease) currently requiring immunosuppressive therapy
- Platelet count < 50 × 10⁹/L, hemoglobin < 80 g/L, international normalized ratio (INR) > 3.0 and not reversible (unless on warfarin with INR within the target range)
- Known bleeding disorders (e.g., hemophilia, von Willebrand disease, acquired von Willebrand syndrome)
- Malignancy diagnosed within the past 5 years (except for cured thyroid cancer, breast cancer, lung cancer, cervical cancer, etc.) and currently receiving chemotherapy, radiotherapy, or targeted therapy
- Prior recipients of heart transplantation or other organ transplants
- Patients awaiting heart transplantation with an anticipated waiting time of less than 3 months
- Pregnant or lactating women
- Reproductive-age women who are capable of conceiving but refuse to use effective contraception during the study period (including surgical sterilization, intrauterine device, oral contraceptives, condoms, etc.)
- Women planning pregnancy during the study
- Known allergy to metformin or any drug excipient
- Known history of lactic acidosis
- Currently using medications that may significantly increase the risk of lactic acidosis, including but not limited to: carbonic anhydrase inhibitors (topiramate, acetazolamide), antiretroviral drugs (especially nucleoside reverse transcriptase inhibitors), certain chemotherapeutic agents (cisplatin)
- Currently using medications that may affect glycemic control or insulin sensitivity and that cannot be stopped or substituted during the study, including but not limited to: systemic glucocorticoids (prednisone-equivalent dose > 10 mg/day for > 2 weeks), high-dose thiazide diuretics (hydrochlorothiazide > 50 mg/day), atypical antipsychotics (olanzapine, clozapine, etc.), immunosuppressants (tacrolimus, cyclosporine, etc.)
- Unable to complete 12-month follow-up
- Known psychiatric disorders or cognitive impairment that may affect informed consent validity or study compliance
- History of drug or alcohol abuse (within the past year)
- Concurrent participation in another clinical trial
- Any other circumstance, as determined by the investigator, that would render the subject unsuitable for enrollment (including but not limited to social, psychological, or geographic factors)
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
China5 sites, 5 recruiting
- Recruiting
The First Affiliated Hospital of Harbin Medical University
Ha’erbin, 150001
Xie, Dr., +8613059008055, baodongxie_doctor@aliyun.com
- Recruiting
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Pan, Dr., +8613732255304, pandihao@zju.edu.cn
- Recruiting
Huai'an Hospital Affiliated to Yangzhou University
Huai'an, 223300
Li, Dr., +8615996187390, hongskj@163.com
- Recruiting
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University
Nanjing, Jiangsu, 210008
Tuo Pan, MD, +8615205160210, pan_tuo@126.com
- Recruiting
Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University
Zhengzhou, 450000
He, Dr., +8613838338095, 13838338095@163.com
About this study
Official title: Study on the Effect of Metformin in Improving Cardiac Function After Implantation of Left Ventricular Assist Devices
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.
Read more
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.
- Conditions
- Heart Failure, Left Ventricular Assist Device
- Being tested
- Metformin Hydrochloride, Placebo
- Keywords
- Metformin, Cardiac Function, LVAD, Randomized Controlled Trial, Full Responder
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
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.
PlaceboDrug
Matching placebo tablets, identical in appearance to metformin, administered orally following the same dose-escalation and maintenance schedule as the active comparator.
| Study group | Role | What they receive |
|---|---|---|
| Metformin Group | Experimental | 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). Receives: Drug: Metformin Hydrochloride |
| Placebo Group | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Full Responder at 12 Months Post-LVAD Implantation
Full Responder is defined as meeting all of the following four criteria at 12 months post-implantation: (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.
Measured: 12 months post-LVAD implantation
Secondary outcomes (33)
Composite of Clinical Adverse Events
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. Each event will be reported separately.
Measured: Up to 24 months post-LVAD implantation
Partial Responder incidence
Incidence of Partial Responder, defined as meeting the Utah-Inova Partial Responder criteria (improvement in left ventricular ejection fraction [LVEF] from baseline ≥5 percentage points, but absolute LVEF remains <40%).
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Composite fibrotic phenotype incidence
Incidence of composite fibrotic phenotype, defined as soluble ST2 (sST2) >100 ng/mL at both 6 months and 12 months AND absolute global longitudinal strain (GLS) <10% at 12 months.
Measured: 6 and 12 months post-LVAD implantation
Change in left ventricular ejection fraction (LVEF)
Change from baseline in LVEF (measured in percentage points).
Measured: 12 months and 24 months post-LVAD implantation
Change in left ventricular end-diastolic diameter (LVEDD)
Change from baseline in LVEDD (measured in millimeters, mm)
Measured: 12 months and 24 months post-LVAD implantation
Change in absolute global longitudinal strain (GLS)
Change from baseline in absolute GLS (measured in percentage, %).
Measured: 12 months and 24 months post-LVAD implantation
Change in soluble ST2 (sST2)
Change from baseline in soluble ST2 (sST2) level. Unit of Measure: ng/mL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in B-type natriuretic peptide (BNP)
Change from baseline in B-type natriuretic peptide (BNP) level. Unit of Measure: pg/mL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in triglyceride-glucose (TyG) index
Change from baseline in TyG index, calculated as Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Unit of Measure: Unitless (index value)
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in fasting glucose
Change from baseline in fasting glucose level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in fasting insulin
Change from baseline in fasting insulin level. Unit of Measure: μU/mL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in HOMA-IR index
Change from baseline in homeostatic model assessment for insulin resistance (HOMA-IR) index, calculated as fasting glucose (mmol/L) × fasting insulin (μU/mL) / 22.5. Unit of Measure: Unitless (index value)
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in hemoglobin A1c (HbA1c)
Change from baseline in HbA1c level. Unit of Measure: %
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in total cholesterol
Change from baseline in total cholesterol level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in triglycerides
Change from baseline in triglyceride level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in HDL-C
Change from baseline in high-density lipoprotein cholesterol (HDL-C) level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in LDL-C
Change from baseline in low-density lipoprotein cholesterol (LDL-C) level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in ALT
Change from baseline in alanine aminotransferase (ALT) level. Unit of Measure: U/L
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in AST
Change from baseline in aspartate aminotransferase (AST) level. Unit of Measure: U/L
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in total bilirubin
Change from baseline in total bilirubin level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in serum creatinine
Change from baseline in serum creatinine level. Unit of Measure: mg/dL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in eGFR
Change from baseline in estimated glomerular filtration rate (eGFR). Unit of Measure: mL/min/1.73m²
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in serum lactate
Change from baseline in serum lactate level. Unit of Measure: mmol/L
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in serum vitamin B12
Change from baseline in serum vitamin B12 level. Unit of Measure: pg/mL
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in 6-minute walk distance (6MWD)
Change from baseline in 6-minute walk distance. Unit of Measure: meters (m)
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in peak oxygen consumption (VO₂max)
Change from baseline in peak oxygen consumption measured by cardiopulmonary exercise testing. Unit of Measure: mL/kg/min
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score
Change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score. The KCCQ is a 23-item self-administered questionnaire that measures physical function, symptoms (frequency and severity), social function, self-efficacy and knowledge, and quality of life in patients with heart failure.
Unit of Measure: Points on a scale. Scale Title: Kansas City Cardiomyopathy Questionnaire Overall Summary Score. Minimum Value: 0. Maximum Value: 100. Higher Score Indicates Better Outcome: Yes
Measured: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Adverse event-related discontinuation rate
Proportion of participants who discontinue the study drug due to adverse events. Unit of Measure: Proportion of participants (%)
Measured: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of lactic acidosis
Incidence of lactic acidosis, defined as serum lactate >5 mmol/L with arterial pH <7.35. Unit of Measure: Proportion of participants (%)
Measured: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of acute kidney injury (AKI)
Incidence of acute kidney injury, defined according to KDIGO criteria. Unit of Measure: Proportion of participants (%)
Measured: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of liver function abnormality
Incidence of liver function abnormality, defined as ALT/AST >3× upper limit of normal or total bilirubin >2× upper limit of normal. Unit of Measure: Proportion of participants (%)
Measured: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of gastrointestinal adverse events
Incidence of gastrointestinal adverse events, including nausea, vomiting, diarrhea, and other related symptoms. Unit of Measure: Proportion of participants (%)
Measured: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of vitamin B12 deficiency
Incidence of vitamin B12 deficiency, defined as serum vitamin B12 <200 pg/mL. Unit of Measure: Proportion of participants (%)
Measured: From baseline through 12 months (treatment period), plus 30 days follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2026
- Study start1 Jul 2026
- Primary completionJul 2028 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07666698
- Sponsor's protocol ID
- CZLB506-2020
- Status last verified
- May 2026
- First submitted
- 22 May 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Effect of Metformin in Improving Cardiac Function After Implantation of Left Ventricular Assist Devices
- ClinicalTrials.gov ID
- NCT07666698
- Acronym / sponsor ID
- CZLB506-2020
- Conditions
- Heart Failure, Left Ventricular Assist Device
- Keywords
- Metformin, Cardiac Function, LVAD, Randomized Controlled Trial, Full Responder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Study start
- 1 Jul 2026 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 24 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin Group | Experimental | Drug: Metformin HydrochlorideMetformin 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 Group | Placebo comparator | Drug: PlaceboMatching 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-75 years
- Receiving continuous-flow LVADs, such as HeartMate 3, HVAD, Core-Heart 6, Brio-Heart
- Presence of insulin resistance
- HbA1c ≤ 6.5%
Key exclusion criteria (42 listed)
- Diagnosed type 1 diabetes mellitus, or type 2 diabetes mellitus with HbA1c > 6.5% (patients with prior type 2 diabetes who are currently off therapy and have HbA1c ≤ 6.5% may be enrolled; such patients may still have insulin resistance but have achieved glycemic control)
- History of diagnosed diabetic ketoacidosis or hyperosmolar hyperglycemic state
- Currently using any glucose-lowering medications (including insulin, oral hypoglycemic agents, GLP-1 receptor agonists, SGLT2 inhibitors, etc.)
- History of diagnosed polycystic ovary syndrome (PCOS) and currently undergoing treatment
- Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m² (CKD-EPI equation)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin HydrochlorideMetformin 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 | Metformin Group |
| PlaceboMatching placebo tablets, identical in appearance to metformin, administered orally following the same dose-escalation and maintenance schedule as the active comparator. | Drug | Placebo Group |
Primary outcome
Incidence of Full Responder at 12 Months Post-LVAD Implantation
Time frame: 12 months post-LVAD implantation
Full Responder is defined as meeting all of the following four criteria at 12 months post-implantation: (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.
33 secondary outcomes
Composite of Clinical Adverse Events
Time frame: Up to 24 months post-LVAD implantation
Partial Responder incidence
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Composite fibrotic phenotype incidence
Time frame: 6 and 12 months post-LVAD implantation
Change in left ventricular ejection fraction (LVEF)
Time frame: 12 months and 24 months post-LVAD implantation
Change in left ventricular end-diastolic diameter (LVEDD)
Time frame: 12 months and 24 months post-LVAD implantation
Change in absolute global longitudinal strain (GLS)
Time frame: 12 months and 24 months post-LVAD implantation
Change in soluble ST2 (sST2)
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in B-type natriuretic peptide (BNP)
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in triglyceride-glucose (TyG) index
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in fasting glucose
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in fasting insulin
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in HOMA-IR index
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in hemoglobin A1c (HbA1c)
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in total cholesterol
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in triglycerides
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in HDL-C
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in LDL-C
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in ALT
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in AST
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in total bilirubin
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in serum creatinine
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in eGFR
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in serum lactate
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in serum vitamin B12
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in 6-minute walk distance (6MWD)
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in peak oxygen consumption (VO₂max)
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score
Time frame: 1, 3, 6, 12, 18, and 24 months post-LVAD implantation
Adverse event-related discontinuation rate
Time frame: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of lactic acidosis
Time frame: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of acute kidney injury (AKI)
Time frame: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of liver function abnormality
Time frame: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of gastrointestinal adverse events
Time frame: From baseline through 12 months (treatment period), plus 30 days follow-up
Incidence of vitamin B12 deficiency
Time frame: From baseline through 12 months (treatment period), plus 30 days follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University
Nanjing, China
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, China
The First Affiliated Hospital of Harbin Medical University
Ha’erbin, China
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Metformin Hydrochloride in people with Heart Failure and Left Ventricular Assist Device, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Full Responder at 12 Months Post-LVAD Implantation (time frame: 12 months post-LVAD implantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.