The Influence of Metformin on Chronic Heart Failure Clinical Course in Patients With Prediabetes

NCT ID: NCT04549415

Last Updated: 2020-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2019-11-15

Brief Summary

It is well known fact, that prediabetes is a predictor of high cardiovascular mortality, increasing the risk of developing such adverse cardiovascular events as myocardial infarction, stroke and sudden cardiac death. The key pathogenetic link in development of carbohydrates metabolism disorders (CMD) is insulin resistance (IR), which is one of the crucial mechanisms for the development and progression of chronic heart failure (CHF). IR disrupts the functioning of the myocardium due to endothelial dysfunction, inflammation, oxidative stress, remodeling and impaired myocardial metabolism. In condition of a combination of CMD and CHF the reverse development of hyperglycemia is also difficult due to hyperactivation of neurohormonal systems - renin-angiotensin-aldosterone system, in particular.

So, drug therapy should neutralize the undesirable metabolic effects of hyperglycemia on the course of CHF, as well as prevent the development of micro- and macrovascular complications.

The study will investigate the ability of metformin to impact on clinical and laboratory (neurohormonal, lipid profiles, renal function) parameters of ischemic etiology heart failure patients with prediabetes, as well as their quality of life and prognosis (incidence of adverse cardiovascular events). These tests will be assessed at the beginning and repeated after one year. At the end of the study we will investigate the difference between lifestyle modification effect and metformin treatment.

The study is funded by Ministry of Education and Science of Kyrgyz Republic.

Detailed Description

This is a single centre trial designed to investigate the benefit, if any, of 12-month metformin 2000 mg/day treatment on clinical course of chronic heart failure in 78 patients with coronary artery disease and impaired glucose tolerance.

Participants will be seen in three occasions: screening, baseline randomization, 6 month, final 12 month, during which clinical and laboratory indicators will be assessed. There will also be three telephone visits at: month 1, month 3, month 9.

At a screening visit an initial history will be performed during following informed consent. Participants will undergo a laboratory, clinical and instrumental screening in Chronic Heart Failure department of National Centre of cardiology and Internal Medicine named after academician M.Mirrakhimov. Among with anthropologic and clinical data, prior to metformin administration, blood samples were evaluated.

Participants who meet all inclusion criteria will return for the randomization during hospitalization to either Metformin or Lifestyle modification alone.

After 6 months of observation safety indicators will be evaluated, as well as fasting and postprandial glucose, creatinine, ECG.

In the active arm, therapy will be metformin in an initial dose of 1000 mg/day (metformin 500 mg х2/day). Participants will continue on Metformin 500 mg x2/day for 2 weeks, following safety blood checks this dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated it will be reduced to 1000 mg/day (or stopped if not tolerated).

The target dose of Metformin at 2000 mg/day was chosen based on previous study of metformin in nondiabetic heart failure patients with IR

Conditions

Chronic Heart Failure; Coronary Artery Disease; PreDiabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

metformin

Metformin, 1000 mg b.i.d, 12 months

Group Type: ACTIVE_COMPARATOR

Metformin Hydrochloride

Intervention Type: DRUG

patients were divided into 2 groups: 1st group was on lifestyle modification (LSM), 2nd group on regimen "LSM+ metformin (1000 g b.i.d)" during 12 months

lifestyle modification

Lifestyle modification Standard Principles

Group Type: ACTIVE_COMPARATOR

lifestyle modification

Intervention Type: OTHER

Lifestyle modification Standard Principles

Interventions

Metformin Hydrochloride

patients were divided into 2 groups: 1st group was on lifestyle modification (LSM), 2nd group on regimen "LSM+ metformin (1000 g b.i.d)" during 12 months

Intervention Type: DRUG

lifestyle modification

Lifestyle modification Standard Principles

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Aged 18 years or over (not older 65 y.o)
• Participant willing and able to give informed consent
• Documented Coronary artery disease (CAD): either angio-graphically documented CAD or a previous history of myocardial infarction/angina.
• Verified heart failure functional class III (Nt-proBNP levels, 6-min walking test)
• Fasting insulin resistance ≥ 2.5 (HOMA-IR)
• Receiving basic therapy for CAD and chronic heart failure (CHF)
• Able (in the investigators opinion) and willing to comply with all study requirements

Exclusion Criteria

• Cognitive impairments
• Type 1 or 2 Diabetes mellitus, antihyperglycemic therapy in anamnesis
• Unstable course of CAD
• Acute heart failure or CHF decompensation
• Malignancy (receiving active treatment) or other life threatening disease
• Renal dysfunction (stage 3B or worse)
• Thyroid dysfunction
• Pregnancy/lactating females
• Any other reason considered inappropriate by a study physician
• Participants who have participated in any other clinical trial within the previous 30 days

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

OTHER_GOV

Sponsor Role: lead

Responsible Party

Bermet Kurmanbekova

Principal investigator, researcher in chronic heart failure department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Akbay Sarybaev

Role: STUDY_DIRECTOR

National Centre of Cardiology and Internal Medicine

Locations

National Centre of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Bishkek, , Kyrgyzstan

Countries

Kyrgyzstan

Other Identifiers

NoruzbaevaCHF

Identifier Type: -

Identifier Source: org_study_id