Clinical trial NCT04549415: The Influence of Metformin on Chronic Heart Failure Clinical Course in Patients With Prediabetes
Official title: The Effect of Metformin on Clinical Course of Ischemic Etiology Chronic Heart Failure in Patients With Prediabetes: the Open-label Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Heart Failure
Coronary Artery Disease
PreDiabetes
Keywords: metformin
chronic heart failure
prediabetes
insulin resistance
clinical course
Lead sponsor: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
Sponsor class: OTHER_GOV
First posted: 2020-09-16
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 12 months
measure: Number of participants with newly diagnosed diabetes mellitus
timeFrame: 12 months
Secondary outcomes:
measure: Chronic heart failure patients Quality of Life
timeFrame: 12 months
measure: 6-minute walking test results
timeFrame: 12 months
measure: Insulin resistance by HOMA-IR
timeFrame: 12 months
measure: Aldosterone levels
timeFrame: 12 months
measure: Nt-proBNP levels
timeFrame: 12 months
measure: Renal function markers
timeFrame: 12 months
measure: Lipid profile markers
timeFrame: 12 months
Other outcomes:
Locations:
city: Bishkek
country: Kyrgyzstan
facility: National Centre of Cardiology and Internal Medicine named after academician M.Mirrakhimov
Study officials:
affiliation: National Centre of Cardiology and Internal Medicine
name: Akbay Sarybaev
role: STUDY_DIRECTOR
References: