Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure

If feasible (run-in of patients into the hospital from 08:00 a.m. to 06:00 p.m.) screening/baseline, enrolment, randomization and first dose of empagliflozin should be performed on the same day. In general, but especially in case of other run-in times (e.g. late evening, night and early morning hours) screening/baseline time period should not exceed 12 hours. In case a patient has to spend the night in hospital before randomization can be executed, a time period of up to 16 hours will not be counted as protocol deviation.

Inclusion criteria

• Patients (age between 18-85 years) with acute decompensated heart failure (HF).
• Brain Natriuretic Peptide (BNP) >100 pg/ml, or N-terminal pro-BNP (NT-proBNP)>300 pg/ml as defined by current clinical guidelines for the diagnosis of acute decompensated HF (European Society of Cardiology 2016 HF guideline)
• Patients with diabetes mellitus type 2 or impaired glucose tolerance as defined by current clinical guidelines (German and International Diabetes Society 2016: HbA1c>6.5 % (upper limit for this clinical trial 12 %) or fasting glucose >7.0 mmol/l or any incidental glucose level >11.1 mmol/l or abnormal oral glucose tolerance test with 2h plasma glucose >7.8 mmol/l) or on antidiabetic medication or antidiabetic diet or patients with normal Glucose tolerance
• Patients without cognitive impairment, i.e. they must be capable of understanding the nature, significance and implications of the clinical trial and to form a rational intention in the light of the facts
• Written informed consent obtained
• For women with childbearing potential (until 2 years after menopause):

• Negative pregnancy test
• regular and correct use of a highly effective contraceptive method with an error rate of <1% per year (e.g. combined (estrogen and progesteron) hormonal contraception (oral, intravaginal, transdermal), progesteron-only hormonal contraception (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS) tubal ligation (female sterilization), hormon donating intrauterine device ("hormonal spiral"), double barrier methods, sexual abstinence, vasectomy of the partner)

Exclusion criteria

• Type 1 diabetes mellitus
• Chronic Kidney Disease (CKD) with eGFR< 30 ml/min, or end-stage renal failure with the need for chronic dialysis treatment
• Acute kidney injury (AKI) ≥ Acute Kidney Injury Network (AKIN) stage 2 or requiring dialysis treatment
• Current medication with SGLT-2 inhibitors
• Known intolerance or hypersensitivity to the active substance empagliflozin, lactose or any other of the excipients listed in section 6.1. of the summary of product characteristics (SmPC). A contraindication or intolerance to furosemide
• Acute heart failure without signs of congestion ("dry" patient)
• Indication for urgent coronary angiography or any planned administration of a iodine based contrast agent within the next 6 days
• Need for hemofiltration or any other form of extracorporeal therapy
• Planned surgery
• Previous participation in this trial or recent participation in another clinical trial (within the last 3 months before inclusion, so that medical product/s from previous trial participation/s have been fully washed out )Identification of any causes of heart failure leading to decompensation that needs urgent management (like acute coronary syndrome, severe unstable arrhythmias, mechanical causes, acute pulmonary embolism)
• Incapacity to understand and / or to provide written informed consent
• Ongoing reported alcohol abuse (daily alcohol intake of more than 2 drinks (liquor, beer or wine) in men and 1 drink in women, corresponding to 12/24 g of pure alcohol per day women / men and/ or obvious alcoholisation of the patient during screening )