Heart failure (HF) with reduced ejection fraction (EF). MedDRA version: 20.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Sponsors
Boehringer Ingelheim International GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in New York Heart Association (NYHA) HF class II-IV - Chronic HF with reduced EF defined as LVEF = 40% per local reading (obtained under stable condition by 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: a) 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, b) 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, c) 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 d) For EF = 40% and documented HHFc within 12 months prior to visit 1, elevated NT-proBNP at Visit 1 = 600 pg/ml for patients without AF and = 1200 pg/ml for patients with AF, analysed at the Central Laboratory. - Appropriate dose of medical therapy for HF (such as ACEi, ARB, ß-blocker, oral diuretics, MRA, ARNI, ivabradine) consistent with prevailing local and international CV guidelines, stable for at least 1 week prior to Visit 1 and during screening period until Visit 2 with exception of diuretics stable for only one week prior to Visit 2 to control symptoms. - 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 implanted within 3 months prior Visit 1, or if intent to implant ICD or CRT 8. Body Mass Index =65 years) yes F.1.3.1 Number of subjects for this age range 1675
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. Heart transplant recipient, or listed for heart transplant 3. Currently implanted left ventricular assist device (LVAD) 4. 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 5. Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial in the investigator’s opinion 6. 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) 7. Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 2 (Randomisation) 8. Untreated ventricular arrhythmia with syncope in patients without ICD documented within the 3 months prior to Visit 1 9. Diagnosis of cardiomyopathy induced by chemotherapy or peripartum within the 12 months prior to Visit 1 10. 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 |
|---|---|
| Main Objective: to demonstrate superiority of empagliflozin 10 mg versus placebo on top of guideline-directed medical therapy in patients with symptomatic, chronic HF and reduced ejection fraction (LVEF = 40%).;Secondary Objective: Not applicable;Primary end point(s): Time to first event of adjudicated CV death or adjudicated HHF in patients with Heart Failure with reduced Ejection Fraction (HFrEF).;Timepoint(s) of evaluation of this end point: Report time to event | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Occurrence of adjudicated HHF (first and recurrent), 2. eGFR (CKD-EPI)cr slope of change from baseline Other secondary endpoints: - Time to first occurrence of chronic dialysis or renal transplant or sustained reduction of =40% eGFR (CKD-EPI) or a) sustained eGFR (CKD-EPI)cr <15 mL/min/1.73 m2 for patients with baseline eGFR =30 mL/min/1.73 m2 b) sustained eGFR (CKD-EPI)cr <10 mL/min/1.73 m2 for patients with baseline eGFR <30 mL/min/1.73 m2 Chronic dialysis is regarded as chronic if the frequency of dialysis is twice or more per week for at least 90 days. - Time to first adjudicated HHF - Time to adjudicated CV death - Time to all-cause mortality - Time to onset of DM (defined as HbA1c =6.5% or as diagnosed by the Investigator) in patients with pre- DM defined as no history of DM and no HbA1c =6.5 before treatment, and a pre-treatment HbA1c value of = 5.7 and <6.5 - Change from baseline in clinical summary score (HF symptoms and physical limitations domains) of the Kansas City Cardiomyopathy Questionnaire (KCCQ) at week 52 - Occurrence of all-cause hospitalisation (first and recurrent) ;Timepoint(s) of evaluation of this end point: Report time to event | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Czech Republic, European Union, France, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Singapore, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactCT Disclosure & Data Transparency
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed