Chronic Heart Failure with reduced Ejection Fraction
Conditions
Interventions
* 4-21 days screening period
* Approximately 20-38 months double-blind treatment until the required number
of adjudicated primary events is reached with empagliflozin or placebo
* Follow-up visit 30 d
Efficacy
Empagliflozin
Heart failure
Safety
Sponsors
Boehringer Ingelheim International GmbH
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Patients with chronic HF diagnosed for at least 3 months before Visit 1, and currently in HF NYHA class II-IV * Chronic HF with reduced EF defined as LVEF * 40% per local reading (obtained under stable condition echocardiography, radionuclide ventriculography, invasive angiography, MRI or CT). A historical LVEF may be used if it was measured within 6 months prior to visit 1 or the LVEF may be measured after study consent has been obtained. The LVEF must be documented in an official report prior to randomization. - In addition to LVEF * 40%, patients must have at least one of the following evidence of HF: - If EF *36 to *40: Elevated NT-proBNP at Visit 1 *2500 pg/ml for patients without AF, OR *5000 pg/ml for patients with AF, analysed at the Central Laboratory, - If EF *31 to *35: Elevated NT-proBNP at Visit 1 *1000 pg/ml for patients without AF, OR *2000 pg/ml for patients with AF, analysed at the Central Laboratory, - If EF*30%: Elevated NT-proBNP at Visit 1 *600 pg/ml for patients without AF, OR *1200 pg/ml for patients with AF, analysed at the Central Laboratory * Appropriate dose of medical therapy for HF (such as ACEi, ARB, *-blocker, oral diuretics, MRA, ARNI, ivabradine) and appropriate device therapy, consistent with prevailing CV guidelines, stable for at least 1 week prior to Visit 1(screening) and during screening period until Visit 2 (Randomisation) with the exception of diuretics stable for only one week prior to Visit 2 to control symptoms. The investigator must document the reason why patient not on target dose per local guidelines. ;* Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, unless it is implanted within 3 months prior to Visit 1, or if there is an intent to implant ICD or CRT * eGFR * 20 mL/min/1.73m2 at Visit 1
Exclusion criteria
Exclusion criteria: * 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 * Heart transplant recipient, or listed for heart transplant * Currently implanted left ventricular assist device (LVAD) * Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction * Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial in the investigator*s opinion * Acute decompensated HF (exacerbation of chronic HF) requiring i.v. diuretics, i.v. inotropes, or i.v. vasodilators, or LVAD within 1 week from discharge to Visit 1 (Screening) and during screening period until Visit 2 (Randomisation) * Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 2 (Randomisation) * Untreated ventricular arrhythmia with syncope in patients without ICD documented within the 3 months prior to Visit 1 * Diagnosis of cardiomyopathy induced by chemotherapy or peripartum within the 12 months prior to Visit 1 * Symptomatic bradycardia or second or third degree heart block without a pacemaker after adjusting beta-blocker therapy, if appropriate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The composite primary endpoint for this trial is the time to first event of adjudicated CV death or adjudicated HHF in patients with HFrEF. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoints which are part of the testing strategy, are the following; * Occurrence of adjudicated HHF (first and recurrent) * eGFR (CKD-EPI)cr slope of change from baseline Other secondary endpoints are: * Time to first occurrence of chronic dialysis or renal transplant or sustained reduction of *40% eGFR (CKD-EPI) or * sustained eGFR (CKD-EPI)cr | — |
Countries
The Netherlands
Outcome results
None listed