Effect of Metformin and Empagliflozin in insulin resistant patients with heart failure with reduced ejection fractio

Phase 1

• Conditions: Heart Failure with reduced ejection fraction (HFrEF and HFmrEF); Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-004149-26-DE
• Lead Sponsor: Charité Universitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-21
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 88

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 <450m,
7.Elevated natriuretic peptides (BNP =100pg/mL or N-terminal-pro-BNP =300 pg/mL),
8.Current standard medication for reduced EF (HFrEF and HFmrEF) therapy according to guideline recommendations in individually optimized doses,
9.Patients need to be free of signs of acute decompensated HF, but can be recruited at the end of a hospital stay, if clinically stabilised,
10.Presence of insulin resistance (e.g. HOMA-IR = 2.0; SPISE index < 6.87 or Quicky index < 0.32)
11.Willing and capable of providing informed consent, participating in all associated study activities

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 88
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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