Heart Failure with reduced ejection fraction (HFrEF and HFmrEF)
Conditions
Interventions
Trade Name: Sifor 1000
Product Name: Metformin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Metformine
CAS Number: 657-24-9
Other descriptive name: METFORMIN HYDROCHLORIDE PH. EUR.
Con
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Written Informed Consent prior to any study related measures 2. Age =18 years, 3. Patients with Symptoms of heart failure (NYHA II-III) in stable ambulatory condition, 4. Patients with the diagnosis of HF for > 6 months 5. Left ventricular ejection fraction (LVEF) =50% , 6. 6-minute walking distance of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.1. Acute decompensated heart failure reduced EF (HFrEF and HFmrEF) requiring acute intravenous therapy or acute dehydration, 2. Current treatment with metformin or empagliflozin 3. Known hypersensitivity or contraindication for Metformin or to any of the excipients of the Investigational Medicinal Product (IMP) or placebo, 4. Type I DM, 5. Diagnosed DM (HbA1c >7.5 or existing medical treatment for DM), 6. Clinical signs or symptoms of dehydration requiring iv volume therapy, 7. impaired kidney function >CKD stage III (GFR <30 ml/min/1.73m2), 8. Acute infection requiring antibiotic therapy, 9. Any clinical condition that limits the life expectancy <1y 10. Incapability to participate in the trial, 11. Acute systemic illness, malignancy, inflammatory disease, requiring, antibiotic therapy, immune-suppressive - or steroid therapy, 12. Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial, 13. Subject with participation in another interventional clinical trial during this study or within 30 days (or longer) before entry into this trial (as a minimum; 5 x elimination half-life / terminal elimination of an IMP), 14. Subjects who are legally detained in an official institution, 15. Subjects who may be dependent on the sponsor, the investigator or the trial sites, have to be excluded from the trial, 16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) urine test, 17. For female patients of reproductive potential: Unwilling to agree to use a highly effective method of contraception (Pearl index <1) throughout the study period, Exclusion criteria that occur in the course of the study do not necessarily lead to study discontinuation. Depending on the exclusion criterion, the investigator may consider interruption or discontinuation of the IMP if it occurs during the course of IMP intake.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Improvement of myocardial contractility and functional capacity in patients with reduced EF (HFrEF and HFmrEF) and insulin resistance in comparison with two control groups (empaglifozin and placebo).;Secondary Objective: Safety aspects of metformin therapy in patients with HFrEF ;Primary end point(s): Change in global longitudinal strain (GLS) of the left ventral (LV) after 24-week therapy. Primary endpoint assessed by Cardiac MR and by echocardiography in patients not eligible for MR.;Timepoint(s) of evaluation of this end point: after 24 weeks therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints (at 24 weeks): • Change in 6min-walking distance • Patient global assessment (PGA) Other secondary endpoints (at 24 and 52 weeks) • Change in 6 min walking distance (52w) • Patient global assessment (52w) • Change in NYHA functional class • Change in Quality of life assessed by EQ5-D and Kansas City Cardiomyopathy Questionnaire (KCCQ) • Change in plasma levels of brain-type natriuretic peptides (BNP) Other exploratory endpoints (at 24 weeks and at 52 weeks), metformin vs. empaliflozin: • Change in echocardiographic measures of LV function and morphology • Change in insulin sensitivity (e.g. HOMA-IR, SPISE index or Quicky index) • Change in MR measures of LV function and structure at rest and under isometric handgrip exercise (MRI-sub-study, 24 weeks only) • Change in myocardial and skeletal muscle triglyceride content assessed by MTG MR Spectroscopy (MRI-sub-study, 24 weeks only) • Change in skeletal muscle phosphocreatinine and ATP levels assessed by 31p MR Spectroscopy • Change in skeletal muscle glycolytic and lipolytic activity (Microdialysis substudy, 24 weeks) • Change in plasma profile of energy substrate metabolites (Lipid profile, FFS, glycerol, pyruvate, ketone bodies, lactate) • Changes in plasma levels of kidney function, liver function and inflammation • Changes in fecal microbiome after metformin vs. Placebo (microbiome substudy) • Decrease of lymphocytic pro-inflammatory mediators after metfomin vs. Placebo ;Timepoint(s) of evaluation of this end point: at week 24 and / or at week 52 | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Wolfram Döhner
Charité Universitätsmedizin
Outcome results
None listed