Metformin in Heart Failure Without Diabetes

NCT03331861 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAR5389
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

A pilot clinical research study that will assess the use of the medication metformin for heart failure in patients who are not diabetic and have no evidence of insulin resistance.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change in Minute Ventilation to Carbon Dioxide Production (VE/VCO2) Slope

  The VO2 change outcomes will be assessed for normality using standard visual assessments (Q-Q plots and histograms) and statistical tests (Kolmogorov-Smirnov). VE/VCO2 slope change will be calculated.

  Baseline and 6 months

Secondary Outcomes (4)

• Change in Visual Analog Scale (VAS) Score

  Baseline and 6 months

• Minnesota LIVING WITH HEART FAILURE Questionnaire (MLHFQ) Score

  Baseline, 6 months

• Peak Myocardial Oxygen Consumption (VO2)

  Baseline, 6 months

• Heart Failure Hospitalizations

  Up to 6 months

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin for 6 months

Drug: Metformin hydrochloride

Placebo

PLACEBO COMPARATOR

Matched placebo for 6 months

Drug: Placebo

Interventions

Metformin hydrochloride DRUG

Metformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months

Also known as: Metformin

Metformin

Placebo DRUG

Similar dosing regime as active comparator

Also known as: Placebo Tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18yrs old
• Patients with chronic heart failure (defined as \>6 months duration) uptitrated to recommended or maximally tolerated dose of ACE-I/ARB (unless contraindicated) and beta-blocker (unless contraindicated). If indicated, an aldosterone receptor antagonist should be given (unless contraindicated). An ICD and/or CRT should be implanted, if indicated. Patients with a CRT device should be treated for \> 3 months.
• Reduced ejection fraction defined as LVEF ≤ 35%
• NYHA-class II or III with stable symptoms for at least the past 3 months
• Renal Function by eGFR ≥ 45 ml/min (MDRD equation) in accordance with FDA guidance on metformin use in CKD(24)
• Non-insulin resistant defined as a fasting insulin resistance index, or HOMA-IR of \<2.7.
• Non-diabetic defined as a HgbA1c \<6.0

You may not qualify if:

• Any oral or injectable hypoglycemic therapy (e.g. insulin, sulfonylureas)
• Known allergy to metformin or major side effects to metformin treatment
• Concomitant use of a carbonic anhydrase inhibitor (such as acetazolamide or topirafmate)
• Heart Failure Hospitalizations in the past 3 months (primary diagnosis on admission is heart failure)
• Acute myocardial infarction, unstable angina or revascularization with prior 3 months at the time of randomization
• Planned coronary revascularization, heart surgery, CRT implantation or other intervention during the study period that would potentially affect the function of the heart
• Significant, uncorrected primary cardiac valve disease, specifically severely stenotic or regurgitant mitral or aortic valves
• Cardiac arrest or life threatening ventricular arrhythmias within the last 3 months (unless treated with an ICD)
• Atrial fibrillation with poorly controlled ventricular rate at rest (\> 110 beats/min)
• Hypertrophic or restrictive cardiomyopathy, infiltrative or storage myocardial disease, active myocarditis, or pericardial disease.
• Planned major surgery within the study period
• Female patients who are pregnant, nursing, or of childbearing potential while not practicing effective chemical contraceptive methods (i.e. oral, implanted, injectable, or transdermal contraceptive hormones; intrauterine device)
• Current abuse of alcohol or drugs
• Life-expectancy of less than 1 year due to co-existing morbid illness
• Liver disease with ALT or AST \>3 times upper normal limit (it is possible to repeat this measurement once within a month)

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

New York Hospital - Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Metformin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Study was terminated early, data was unblinded but not analyzed due to low enrollment and lack of statistical power.

Results Point of Contact

• Title: Barry Fine, MD
• Organization: Columbia University Irving Medical Center

bmf2002@cumc.columbia.edu

212-305-5755

Study Officials

• Barry Fine, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 1, 2017
• First Posted: November 6, 2017
• Study Start: February 15, 2019
• Primary Completion: August 20, 2021
• Study Completion: August 20, 2021
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-07

Locations

US (1)