Efficacy of Metformin as add-on Therapy in Non-Diabetic Heart Failure Patients

NCT05177588 | Completed Phase 4

• 1 other identifier: CL (2582)
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

There is an increasing interest in the use of metformin in CV diseases and there is an increasing interest in studying its potential new roles in heart failure patients. There were some concerns related to the safety of metformin in such diabetic patients due to the risk of lactic acidosis. However, recent studies showed that metformin was safe or even beneficial in HF patients. We hypothesized that metformin might improve morbidity, mortality, cardiac function, and HR-QoL in non-diabetic patients with HFrEF.

Conditions

Heart Failure

Keywords

Metformin; Heart failure; Non-diabetic; left ventricular mass index

Outcome Measures

Primary Outcomes (3)

• Change in total antioxidant capacity (relative and absolute)

  Change Total antioxidant capacity as assessed by colorimetric assay

  6 months

• Change in Malondialdehyde (MDA)

  Change in Malondialdehyde (MDA) as assessed by colorimetric assay

  6 months

• Chagne in left ventricular mass index

  Chagne in left ventricular mass index as assessed by Echocardiography

  6 months

Secondary Outcomes (6)

• Chagne in Ejection Fraction

  6 months

• New York Heart Association functional classification (NYHA):

  6 months

• TAC

  6 months

• MDA

  6 months

• Adverse reactions of metformin

  6 months

Study Arms (2)

Metformin

EXPERIMENTAL

Patients in the metformin group will receive a starting dose of 1000 mg/day. The dose will be titrated as tolerated to a maximum of 2000 mg/. Patients will receive the medications for six year and will be followed up for the duration of the study. Patients will be assessed at baseline, 3 months, and 6 months.

Drug: Metformin Hydrochloride

Standard of Care

NO INTERVENTION

Patients in the control arm will continue the SOC medications

Interventions

Metformin Hydrochloride DRUG

Metformin 2000 mg/day

Also known as: Glucophage, Cidophage

Metformin

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic heart failure (\>6 months duration)
• Stabilized on recommended or maximally tolerated dose of ACE-I/ARB or ARNI (unless contraindicated) and beta-blocker (unless contraindicated). If indicated, an aldosterone receptor antagonist should be given (unless contraindicated).
• Reduced ejection fraction defined as LVEF \< 45%
• NYHA-class II or III or IV with stable symptoms for at least the past 3 months
• Creatinine clearance \> 45 ml/min

You may not qualify if:

• Diabetes mellitus: Diabetes will be diagnosed using the 2018 The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes 15
• FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.\*
• h PG ≥200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.
• A1C ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.\*
• In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L).
• Any oral or injectable hypoglycemic therapy (e.g. insulin, sulfonylureas)
• Recent Hospitalizations in the past 3 months
• Metformin treatment within the last 3 months
• Creatinine clearance below 45 in the prior 6 months as assessed by Cockcroft and Gault equation
• Known allergy to metformin or major side effects to metformin treatment
• Atrial fibrillation with poorly controlled ventricular rate at rest (\> 100 beats/min)
• Hypertrophic cardiomyopathy

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Agouza Hospital

Giza, 12566, Egypt

Location

Related Publications (4)

• Larsen AH, Jessen N, Norrelund H, Tolbod LP, Harms HJ, Feddersen S, Nielsen F, Brosen K, Hansson NH, Frokiaer J, Poulsen SH, Sorensen J, Wiggers H. A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes. Eur J Heart Fail. 2020 Sep;22(9):1628-1637. doi: 10.1002/ejhf.1656. Epub 2019 Dec 21.

  PMID: 31863557 BACKGROUND

• Mohan M, Al-Talabany S, McKinnie A, Mordi IR, Singh JSS, Gandy SJ, Baig F, Hussain MS, Bhalraam U, Khan F, Choy AM, Matthew S, Houston JG, Struthers AD, George J, Lang CC. A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial. Eur Heart J. 2019 Nov 1;40(41):3409-3417. doi: 10.1093/eurheartj/ehz203.

  PMID: 30993313 BACKGROUND

• Kamel AM, Ismail B, Abdel Hafiz G, Sabry N, Farid S. Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial. Metab Syndr Relat Disord. 2024 Feb;22(1):49-58. doi: 10.1089/met.2023.0164. Epub 2023 Oct 10.

  PMID: 37816240 DERIVED

• Kamel AM, Ismail B, Abdel Hafiz G, Sabry N, Farid S. Total Antioxidant Capacity and Prediabetes Are Associated with Left Ventricular Geometry in Heart-Failure Patients with Reduced Ejection Fraction: A Cross-Sectional Study. Metab Syndr Relat Disord. 2023 Jun;21(5):282-291. doi: 10.1089/met.2023.0019. Epub 2023 May 23.

  PMID: 37220008 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Metformin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Ahmed M Kamel, MSc.

  Faculty of Pharmacy, Cairo University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Model Details: This is a prospective, interventional, randomized controlled, open label study. The study sample will include heart failure patients with pre-diabetes

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 4, 2022
• Study Start: July 21, 2021
• Primary Completion: March 30, 2023
• Study Completion: April 30, 2023
• Last Updated: July 19, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)