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Heart FailurePhase 4NCT05177588

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

A Phase 4 study testing Metformin Hydrochloride in people with Heart Failure, run by Cairo University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Heart Failure
What is being tested?
Metformin Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteEgypt
Study dates
21 Jul 2021to 30 Apr 2023
Phase
Phase 4
Are there results?
None posted in the registry

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 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.*
  • 2-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)
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Egypt1 site

  • Agouza Hospital

    Giza, 12566

Other trials in Egypt

About this study

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.

Read the detailed description

Metformin is an anti-diabetic drug that is known improve insulin sensitivity and reduce insulin resistance. A published meta-analysis of randomized controlled trials (RCTs) reported a reduction of weight and insulin resistance in metformin users. Animal models also showed that metformin reduces cardiac hypertrophy. Observational studies showed a beneficial effect for metformin in patients with type 2 diabetes mellitus (T2DM) and heart failure. A recent study found that metformin reduced oxidative stress in non-diabetic patients with CAD.

Metformin has multiple modes of actions involving both AMP-activated protein kinase (AMPK) dependent and AMPK-independent mechanisms that may be implicated in cardiac hypertrophy. At the systemic level, a review of clinical and experimental data showed that metformin improves endothelial function, protects from oxidative stress and inflammation, as well as the negative effects of angiotensin II. Observational studies also reported cardiovascular benefits in metformin users especially in patients with type 2 diabetes mellitus (T2DM) and heart failure. Metformin has also been shown to exert a cardio protective effect and it has been shown to reduce oxidative stress which is a common finding in heart failure patients. For these reasons, 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 this aspect. We hypothesized that metformin might improve morbidity, mortality, cardiac function, and HR-QoL in non-diabetic patients with HFrEF.

Conditions
Heart Failure
Being tested
Metformin Hydrochloride
Keywords
Metformin, Heart failure, Non-diabetic, left ventricular mass index
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

    Also called Glucophage, Cidophage

    Metformin 2000 mg/day

Study groups in NCT05177588
Study groupRoleWhat they receive
MetforminExperimentalPatients 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.
Receives: Drug: Metformin Hydrochloride
Standard of CareNo interventionPatients in the control arm will continue the SOC medications

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in total antioxidant capacity (relative and absolute)

    Change Total antioxidant capacity as assessed by colorimetric assay

    Measured: 6 months

  2. Change in Malondialdehyde (MDA)

    Change in Malondialdehyde (MDA) as assessed by colorimetric assay

    Measured: 6 months

  3. Chagne in left ventricular mass index

    Chagne in left ventricular mass index as assessed by Echocardiography

    Measured: 6 months

Secondary outcomes (6)

  1. Chagne in Ejection Fraction

    Ejection fraction as assessed by echocardiography

    Measured: 6 months

  2. New York Heart Association functional classification (NYHA):

    The NYHA classifies patients in one of four possible categories based on the physical activity limitations; the limitations/symptoms are in regards to normal breathing andvarying degrees in shortness of breath and or angina pain

    Measured: 6 months

  3. TAC

    Total antioxidant capacity as assessed by colorimetric assay

    Measured: 6 months

  4. MDA

    MDA as assessed by colorimetric assay

    Measured: 6 months

  5. Adverse reactions of metformin

    Incidence of lactic acidosis

    Measured: 6 months

  6. Change in fasting blood glucose (FBG)

    Change in FBG from baseline

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2022
  2. Study start21 Jul 2021
  3. Primary completion30 Mar 2023
  4. Study completion30 Apr 2023

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a prospective, interventional, randomized controlled, open label study. The study sample will include heart failure patients with pre-diabetes
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05177588
Sponsor's protocol ID
CL (2582)
Status last verified
Jul 2023
First submitted
16 Dec 2021
Last updated
19 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31863557

  • 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.

    PubMed 30993313

  • 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.

    PubMed 37816240

  • 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.

    PubMed 37220008

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Metformin Hydrochloride in people with Heart Failure, run by Cairo University at 1 site in Egypt.

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 5 inclusion and 12 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: finished, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in total antioxidant capacity (relative and absolute) (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05177588, which also lists 4 linked publications.

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 19 Jul 2023.

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