Chronic Heart Failure with reduced Ejection Fraction (HFrEF) MedDRA version: 20.0 Level: LLT Classification code 10078289 Term: Heart failure with reduced ejection fraction System Organ Class: 100000004849
Conditions
Sponsors
Boehringer Ingelheim RCV GmbH & Co KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Of full age of consent (according to local legislation, usually = 18 years) at screening. 2. Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. 3. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial 4. 6MWT distance =350 m at screening and at baseline. 5. Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in NYHA class II-IV 6. Chronic HF with reduced EF defined as LVEF = 40 % as per echocardiography at Visit 1 as per local reading (obtained under stable condition). 7. Elevated NT-proBNP > 450 pg/ml for patients without atrial fibrillation (AF) OR NT-proBNP > 600 pg/ml for patients with AF as analysed at the Central laboratory at Visit 1 8. Patients must be clinically stable and on appropriate and stable dose of medical therapy for HF (such as ACEi, ARB, ß-blocker, oral diuretics, MRA, ARNI, ivabradine), consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at least two weeks prior to Visit 1. The investigator must document the reason in case the patient is not on such medication or if not on target dose of any heart failure medication as per local guidelines. 9. Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement). 10. Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, and if a device is required, it must have been implanted for at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD. 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 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to Visit 1 2. Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 4 weeks prior to Visit 1, and/or during screening period until Visit 2 3. Previous or current randomization in another Empaglifozin Heart Failure trial (i.e. studies 1245.110, 1245.121, 1245-0167) 4. Type 1 Diabetes Mellitus (T1DM) 5. Impaired renal function, defined as eGFR 160mmHg at both Visit 1 and 2 8. Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 1 (Screening) 9. Unstable angina pectoris in past 30 days prior to Visit 1 10. Largest distance walked in 6 minutes (6MWTD) at baseline <100m. 11. Any presence of condition that precludes exercise testing such as: - claudication, - uncontrolled (according to investigator judgement) bradyarrhythmia or tachyarrhythmia, - significant musculoskeletal disease, - primary pulmonary hypertension, - severe obesity (body mass index =40.0 kg/m2), - orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries) - amputation with artificial limb without stable prosthesis function for the past 3 months - Any condition that, in the opinion of the investigator, would contraindicate the assessment of 6MWT 12. Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial. 13. Planned implantation of ICD or CRT during the course of the trial. 14. Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening 15. Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening 16. Further exclusion criteria applies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the effect of empagliflozin 10 mg versus placebo on exercise ability using the 6 minute walk test in patients with chronic HF with reduced ejection fraction (LVEF = 40%);Secondary Objective: Secondary objectives are to assess Patient-Reported Outcome (PRO);Primary end point(s): 1. The primary endpoint is the change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions;Timepoint(s) of evaluation of this end point: 1. Week 0 and Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline to week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS) 2. Change from baseline to week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized format (CHQ-SAS) dyspnea score 3. Change from baseline to week 6 in exercise capacity as measured by the distance walked in 6 minutes 4. Change from baseline in Clinical Congestion Score at week 12 5. Change from baseline in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms at week 12 6. Change from baseline in Patient Global Impression of Dyspnea Severity at week 12 7. Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at week 12 8. Patient Global Impression of Change in Dyspnea at week 12 9. Change from baseline in N-terminal pro-brain natriuretic peptide (NTproBNP) at week 12;Timepoint(s) of evaluation of this end point: 1. Week 0 and Week 12 2. Week 0 and Week 12 3. Week 0 and Week 6 4. Week 0 and Week 12 5. Week 0 and Week 12 6. Week 0 and Week 12 7. Week 12 8. Week 12 9. Week 0 and Week 12 | — |
Countries
Canada, Germany, Greece, Italy, Norway, Poland, Portugal, Spain, Sweden, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed