METFORMIN FOR ATRIAL FIBRILLATION

NCT05878535 | Unknown Phase 2 DMC

• 1 other identifier: #18101829
• Study Type: interventional
• Target: 770
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this multicenter, pragmatic, open-label, randomized, placebo-controlled clinical trial is to test whether repurposing metformin for the treatment of atrial fibrillation will be effective in decreasing patients' hospitalization, adverse major cardiovascular events, and non-cancer death. Participants will be randomized into 2 study arms (385 participant each), whereby:

• The Metformin Group (MG): will receive metformin oral tablets in addition to the standard rate/rhythm control strategy and anticoagulation.
• The Placebo Control Group (PCG): will receive placebo oral tablets as a control group in addition to the standard rate/rhythm control strategy and anticoagulation. Then both arms will be compared according to the these endpoints:
• The primary endpoint is hospitalization due to an episodic AF or an AF with a rapid or slow ventricular response (in the case of permanent AF).
• The secondary endpoint is a composite of non-fatal major cardiovascular adverse events or non-cancer death. The non-fatal major cardiovascular adverse events include:
• Hospitalization due to heart failure.
• Non-fatal myocardial infarction.
• Non-fatal stroke.
• Hospitalization due to unstable angina.

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation, metformin, MACE.

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint

  The primary endpoint is hospitalization due to an episodic AF or an AF with a rapid or slow ventricular response (in the case of permanent AF).

  12 months since randomization

Secondary Outcomes (1)

• Secondary Endpoint

  12 months since randomization

Study Arms (2)

The Metformin Group (MG)

ACTIVE COMPARATOR

The group (n=385) will receive metformin oral tablets in addition to the standard rate/rhythm control strategy and anticoagulation. • Drug: metformin 850 mg oral tablets. Prescribed: Once daily PO with meals and 200 mL of water. The dose can be up-titrated to 1500-2000 mg divided q8-12hr with meals in enrolled diabetic patients as a monotherapy or combined with sulfonylurea. Other Name: Glucophage.

Drug: Metformin

The Placebo Control Group (PCG)

PLACEBO COMPARATOR

The group (n=385) will receive placebo oral tablets in addition to the standard rate/rhythm control strategy and anticoagulation. • Drug: Placebo oral tablets. Prescribed: Once daily PO with meals and 200 mL of water. Other Name: Placebo

Drug: Placebo

Interventions

Metformin DRUG

Metformin 850 mg oral tablets. Prescribed: Once daily PO with meals and 200 mL of water. The dose can be up-titrated to 1500-2000 mg divided q8-12hr with meals in enrolled diabetic patients as a monotherapy or combined with sulfonylurea.

Also known as: Glucophage, Glumetza, and Riomet.

The Metformin Group (MG)

Placebo DRUG

Placebo oral tablets. Prescribed: Once daily PO with meals and 200 mL of water.

The Placebo Control Group (PCG)

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent prior to performing study procedures.
• Atrial fibrillation (first detected, paroxysmal, persistent, longstanding persistent, or permanent)\*.
• \* Types of atrial fibrillation:
• First detected: only one diagnosed episode.
• Paroxysmal: recurrent episodes that stop on their own in less than seven days.
• Persistent: recurrent episodes that last more than seven days.
• Longstanding persistent: recurrent episodes that last more than twelve months.
• Permanent: atrial fibrillation that has been accepted, and for which a solely rate control strategy has been decided upon.

You may not qualify if:

• Critically-ill patients who are admitted to ICU.
• Advanced congestive heart failure.
• Liver cell failure.
• Chronic kidney disease with eGFR \<45 mL/min/1.73 m².
• Diabetic ketoacidosis with or without coma.
• Concomitant treatment with carbonic anhydrase inhibitors.
• Septicemia.
• Shock.
• Hypoxia.
• Dehydration.
• Blood Dyscrasias.
• Alcoholism.
• Pregnancy.
• Lactation.
• Chronic muscle diseases.

Sponsors & Collaborators

• Arab Contractors Medical Centre: lead

Study Sites (1)

Arab Contractors Medical Centre

Cairo, Egypt

Location

Related Publications (8)

• Chung MK, Eckhardt LL, Chen LY, Ahmed HM, Gopinathannair R, Joglar JA, Noseworthy PA, Pack QR, Sanders P, Trulock KM; American Heart Association Electrocardiography and Arrhythmias Committee and Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Lifestyle and Cardiometabolic Health. Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association. Circulation. 2020 Apr 21;141(16):e750-e772. doi: 10.1161/CIR.0000000000000748. Epub 2020 Mar 9.

  PMID: 32148086 BACKGROUND

• Schwaerzer G. Repurposing metformin for treatment of atrial fibrillation. Nat Cardiovasc Res. 2022 Nov;1(11):972. doi: 10.1038/s44161-022-00170-1. No abstract available.

  PMID: 39195908 BACKGROUND

• Lal JC, Mao C, Zhou Y, Gore-Panter SR, Rennison JH, Lovano BS, Castel L, Shin J, Gillinov AM, Smith JD, Barnard J, Van Wagoner DR, Luo Y, Cheng F, Chung MK. Transcriptomics-based network medicine approach identifies metformin as a repurposable drug for atrial fibrillation. Cell Rep Med. 2022 Oct 18;3(10):100749. doi: 10.1016/j.xcrm.2022.100749. Epub 2022 Oct 11.

  PMID: 36223777 BACKGROUND

• Vinciguerra M, Olier I, Ortega-Martorell S, Lip GYH. New use for an old drug: Metformin and atrial fibrillation. Cell Rep Med. 2022 Dec 20;3(12):100875. doi: 10.1016/j.xcrm.2022.100875.

  PMID: 36543101 BACKGROUND

• Donertas HM, Fuentealba Valenzuela M, Partridge L, Thornton JM. Gene expression-based drug repurposing to target aging. Aging Cell. 2018 Oct;17(5):e12819. doi: 10.1111/acel.12819. Epub 2018 Aug 9.

  PMID: 29959820 BACKGROUND

• Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016 Jun 14;23(6):1060-1065. doi: 10.1016/j.cmet.2016.05.011.

  PMID: 27304507 BACKGROUND

• Ostropolets A, Elias PA, Reyes MV, Wan EY, Pajvani UB, Hripcsak G, Morrow JP. Metformin Is Associated With a Lower Risk of Atrial Fibrillation and Ventricular Arrhythmias Compared With Sulfonylureas: An Observational Study. Circ Arrhythm Electrophysiol. 2021 Mar;14(3):e009115. doi: 10.1161/CIRCEP.120.009115. Epub 2021 Feb 7.

  PMID: 33554609 BACKGROUND

• Nantsupawat T, Wongcharoen W, Chattipakorn SC, Chattipakorn N. Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient. Cardiovasc Diabetol. 2020 Nov 24;19(1):198. doi: 10.1186/s12933-020-01176-4.

  PMID: 33234131 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Metformin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Eslam Abbas, MBBCh, MSC

  Arab Contractors Medical Centre, and Dar El Salam Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eslam Abbas, MBBCh, MSC

CONTACT

+201023054574; islam.omr@med.au.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Invstigator

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: May 26, 2023
• Study Start: June 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: April 1, 2025
• Last Updated: January 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data that underlie the results reported in this study will be available upon publication.
• Access Criteria: Data can be shared with researchers who submit a proposal with a valuable research question.

Locations

EG (1)