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Age ≥18 years at screening |
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Male or female patients. WOCBP must be ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly |
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Patients with chronic HF diagnosed for at least 3 months before Visit 1, and currently in HF NYHA class II-IV |
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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). The EF must have been obtained and documented at Visit 1, or within 6 months prior to Visit 1 |
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Patient must have at least one of the following evidence of HF |
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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 |
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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 |
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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 |
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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 (Randomisation) with the exception of diuretics stable for only one week prior to Visit 2 to control symptoms |
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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 |
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Body Mass Index (BMI) > 45 kg/m2 at Visit 1 (Screening) |
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Signed and dated written ICF in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial |
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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
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Heart transplant recipient, or listed for heart transplant
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Currently implanted left ventricular assist device (LVAD)
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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
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Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial in the investigator’s opinion
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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)
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Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 2 (Randomisation)
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Untreated ventricular arrhythmia with syncope in patients without ICD documented within the 3 months prior to Visit 1
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Diagnosis of cardiomyopathy induced by chemotherapy or peripartum within the 12 months prior to Visit 1
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Symptomatic bradycardia or second or third degree heart block without a pacemaker after adjusting beta-blocker therapy, if appropriate
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Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 2. If SBP >150mmHg and <180mmHg at Visit 2, the patient should be receiving at least 3 antihypertensive drugs
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Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 or Visit 2
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Chronic pulmonary disease requiring home oxygen, oral steroid therapy or hospitalisation for exacerbation within 12 months, or significant chronic pulmonary disease in the opinion of the investigator, or primary pulmonary arterial hypertension
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Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1
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Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis, as determined at Visit 1
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Haemoglobin (HgB) <9 g/dl at Visit 1
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History of ketoacidosis
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Major surgery (major according to the investigator’s assessment) performed within 90 days prior to Visit 1, or scheduled major elective surgery (e.g. hip replacement) within 90 days after Visit 1
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Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption in the investigator’s opinion
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Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or low risk prostate cancer (patients with pre-treatment PSA < 10 ng/mL, and biopsy Gleason score of ≤ 6 and clinical stage T1c or T2a)
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Presence of any other disease than heart failure with a life expectancy of <1 years in the opinion of the investigator
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Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
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Treatment with any SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor within 1 week prior to Visit 1 or during screening period until Visit 2 (Randomisation)
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Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded
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Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors
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Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes them an unreliable trial subject or unlikely to complete the trial
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Women who are pregnant, nursing, or who plan to become pregnant while in the trial
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Any other clinical condition that would jeopardise patients safety while participating in this trial, or may prevent the subject from adhering to the trial protocol
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