Empagliflozin in Acute Heart Failure

• Empagliflozin 25 MG (Drug), also known as Jardiance (DIN: 02443945): Patients who fulfill the inclusion criteria will receive an intravenous dose of 1.0-1.5 mg/kg of furosemide (≤120 mg) and urine output will be monitored for three hours. Those with a urine output < 300 ml in the first two hours post furosemide administration will receive a single oral dose of 25 mg of empagliflozin. Two hours after taking empagliflozin, patients will receive a second intravenous dose of 1.0-1.5 mg/kg of furosemide with another timed urine collection at three hours. Empagliflozin will then be continued daily for five days or until hospital discharge, unless the treating physician considers this not to be clinically appropriate.

Primary outcomes

• Diuretic effect of empagliflozin in association with furosemide [Day 1]: Three-hour urine output post empagliflozin-furosemide administration, compared with furosemide alone

Secondary outcomes

• Fractional excretion of sodium in the urine [Day 1]: FeNa (%)
• Total urine sodium output [Day 1-5]: Urine sodium per 24h
• Changes in volume status [Day 1-5]: Net fluid balance
• Incidence of AKI [Day 1-5]: Using the conventional KDIGO criteria
• Electrolyte abnormalities - Sodium [Day 1-5]: Concentration of sodium
• Electrolyte abnormalities - Potassium [Day 1-5]: Concentration of potassium
• Electrolyte abnormalities - Magnesium [Day 1-5]: Concentration of magnesium

Sex: All, ages: 18 Years to any

Inclusion Criteria (all have to apply) :

* moderate to advanced CKD, defined as an eGFR <45 ml/min/1.73m2; The average creatinine values over the last 12 months will be used to calculate baseline eGFR.
* acutely decompensated heart failure, defined as dyspnea at rest or with minimal physical activity, associated with at least one clinical sign of congestion and at least one objective measure of heart failure (pulmonary-capillary wedge pressure >20 mm Hg or evidence of pulmonary congestion on chest radiography or brain natriuretic peptide (BNP) level ≥400 pg/ml or N-terminal pro-BNP level ≥1000 pg/ml);
* evidence of inadequate response to loop diuretics, defined as a urine output < 1000 ml/24h or a weight loss < 1kg /24h. For patients who have not received loop diuretics, a furosemide stress test can be conducted.
* stable hemodynamics, defined as systolic blood pressure >90 mmHg and/or mean arterial pressure >65 mmHg in the absence of intravenous norepinephrine or epinephrine in the last 24 hours.

Exclusion Criteria:

* new use of a non-loop diuretic other than an MRA
* history of type 1 diabetes mellitus
* euglycemic diabetic ketoacidosis
* liver disease defined by serum levels of transaminases or alkaline phosphatase more than three times the upper limit of normal at screening
* known hypersensitivity to SGLT-2 inhibitors
* use within the last 48 h of an SGLT-2 inhibitor or a combined SGLT-1 and SGLT-2 inhibitor
* maintenance dialysis or need for emergent renal replacement therapy
* gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption
* recurrent severe genital or urinary tract infection
* pregnancy or breastfeeding
* any other clinical condition that would jeopardize patient safety while participating in this trial
* Patients with an acute rise in creatinine levels (acute cardiorenal syndrome) upon presentation will not be excluded.

• Thomas Mavrakanas, MD, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre