Chronic Heart FailurePhase 4NCT04549415
The Influence of Metformin on Chronic Heart Failure Clinical Course in Patients With Prediabetes
A Phase 4 study testing Metformin Hydrochloride and lifestyle modification in people with Chronic Heart Failure and Coronary Artery Disease, run by National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov at 1 site in Kyrgyzstan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Heart Failure, Coronary Artery Disease, PreDiabetes
- What is being tested?
- Metformin Hydrochloride and lifestyle modification
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 1 siteKyrgyzstan
- Study dates
- 1 Jan 2018to 15 Nov 2019
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Kyrgyzstan1 site
National Centre of Cardiology and Internal Medicine named after academician M.Mirrakhimov
Bishkek, 720001
About this study
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
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.
Read more
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.
Read the 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
- Being tested
- Metformin Hydrochloride, lifestyle modification
- Keywords
- metformin, chronic heart failure, prediabetes, insulin resistance, clinical course
- Medical subject headings
- Coronary Artery Disease, Prediabetic State, Insulin Resistance, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
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 modificationOther
Lifestyle modification Standard Principles
| Study group | Role | What they receive |
|---|---|---|
| metformin | Active comparator | Metformin, 1000 mg b.i.d, 12 months Receives: Drug: Metformin Hydrochloride |
| lifestyle modification | Active comparator | Lifestyle modification Standard Principles Receives: Other: lifestyle modification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
Safety and efficacy of Metformin will be determined by monitoring changes from randomization till the end of the study or so long the patient remains in the study , whichever is earlier
Measured: 12 months
Number of participants with newly diagnosed diabetes mellitus
Carbohydrate metabolism indicators will be determined by monitoring changes in fasting, postprandial glycemia and glycated hemoglobin
Measured: 12 months
Secondary outcomes (7)
Chronic heart failure patients Quality of Life
Minnesota Living with Heart Failure Questionnaire will be evaluated at baseline and at 12 months
Measured: 12 months
6-minute walking test results
The test is based on measuring the walking distance with turns along a long corridor (≥30 m) at the patient's own pace. Results will be evaluated at baseline and at 12 months
Measured: 12 months
Insulin resistance by HOMA-IR
Improvement in insulin (insulin resistance by HOMA-IR) when treated with metformin compared to lifestyle modification in patients with ischemic etiology CHF and prediabetes using ELISA
Measured: 12 months
Aldosterone levels
Improvement in aldosterone levels when treated with metformin compared to lifestyle modification in patients with ischemic etiology CHF and prediabetes using ELISA
Measured: 12 months
Nt-proBNP levels
Improvement in Nt-proBNP levels when treated with metformin compared to lifestyle modification in patients with ischemic etiology CHF and prediabetes using ELISA
Measured: 12 months
Renal function markers
Creatinine levels with estimated glomerular filtration rate and daily proteinuria at a baseline and at 12 months to assess safety and influence of metformin
Measured: 12 months
Lipid profile markers
Improvement in lipid profile indicators (total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides) when treated with metformin compared to lifestyle modification
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start1 Jan 2018
- Primary completion1 Nov 2018
- Study completion15 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Bermet Kurmanbekova, National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
- Investigators
- Akbay Sarybaev, Study director, National Centre of Cardiology and Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549415
- Sponsor's protocol ID
- NoruzbaevaCHF
- Status last verified
- Sep 2020
- First submitted
- 3 Sep 2020
- Last updated
- 16 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04549415
- Acronym / sponsor ID
- NoruzbaevaCHF
- Conditions
- Chronic Heart Failure, Coronary Artery Disease, PreDiabetes
- Keywords
- metformin, chronic heart failure, prediabetes, insulin resistance, clinical course
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- National Center of Cardiology and Internal Medicine named after academician M.MirrakhimovOther government
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 15 Nov 2019 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| metformin | Active comparator | Drug: Metformin HydrochlorideMetformin, 1000 mg b.i.d, 12 months |
| lifestyle modification | Active comparator | Other: lifestyle modificationLifestyle modification Standard Principles |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin Hydrochloridepatients 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 | Drug | metformin |
| lifestyle modificationLifestyle modification Standard Principles | Other | lifestyle modification |
Primary outcome
Number of participants with adverse events
Time frame: 12 months
Safety and efficacy of Metformin will be determined by monitoring changes from randomization till the end of the study or so long the patient remains in the study , whichever is earlier
Number of participants with newly diagnosed diabetes mellitus
Time frame: 12 months
Carbohydrate metabolism indicators will be determined by monitoring changes in fasting, postprandial glycemia and glycated hemoglobin
7 secondary outcomes
Chronic heart failure patients Quality of Life
Time frame: 12 months
6-minute walking test results
Time frame: 12 months
Insulin resistance by HOMA-IR
Time frame: 12 months
Aldosterone levels
Time frame: 12 months
Nt-proBNP levels
Time frame: 12 months
Renal function markers
Time frame: 12 months
Lipid profile markers
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Akbay Sarybaev study director
National Centre of Cardiology and Internal Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin Hydrochloride and lifestyle modification in people with Chronic Heart Failure and Coronary Artery Disease, run by National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov at 1 site in Kyrgyzstan.
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 7 inclusion and 10 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 16 Sep 2020. 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 Kyrgyzstan. 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?
Number of participants with adverse events (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2020.