The renal and metabolic outcomes after sodium-glucose cotransporter 2 inhibitor in cardiac surgery – an open-label phase IV randomized controlled trial

INTERVENTION: Trade Name: Jardiance Pharmaceutical Form: Film‐coated tablet CONDITION: Cardiac surgery‐associated acute kidney injury ; MedDRA version: 20.1 Level: LLT Classification code 10080266 Term: Stage 1 acute kidney injury System Organ Class: 100000004857 Therapeutic area: Diseases [C] ‐ Symptoms and general pathology [C23] PRIMARY OUTCOME: Main Objective: To investigate the potential of preoperative initiation (7 days) and perioperative continuation (until day 2 after surgery) of empagliflozin 10 mg daily to reduce the acute kidney injury marker neutrophil gelatinase‐associated lipocalin (NGAL) on day 2 postoperatively in patients undergoing cardiopulmonary bypass surgery. Primary end point(s): • Neutrophil gelatinase‐associated lipocalin (NGAL) concentration in plasma on postoperative day 2. Secondary Objective: • To investigate the potential of empagliflozin to reduce perioperative markers of kidney injury (NGAL, KIM‐1) in patients undergoing cardiopulmonary bypass surgery.; • To investigate the potential of empagliflozin to preserve kidney function (eGFR) in patients undergoing cardiopulmonary bypass surgery.; • To assess the effect of empagliflozin on perioperative glycaemia and incidence of hypoglycemia in patients undergoing cardiopulmonary bypass surgery.; • To assess the effect of empagliflozin on perioperative ketonemia and the occurrence of ketoacidosis in patients undergoing cardiopulmonary bypass surgery. Timepoint(s) of evaluation of this end point: • Measured on morning of postoperative day 2, between 8:00 and 12:00. SECONDARY OUTCOME: Secondary end point(s): • Neutrophil gelatinase‐associated lipocalin (NGAL) concentration in plasma.; • Kidney Injury Molecule‐1 (KIM‐1) in plasma.; • Estimated Glomerular Filtration Rate (eGFR) based on plasma creatinine measurements.; • Blood ketone levels.; • Incidence of keto‐acidosis defined as combination of blood ketone concentration >3mmol/l in combination with high‐anion gap acidosis ([Na+]‐[Cl‐]‐[HCO3‐]>12).; • Perioperative peak and average blood glucose levels, as measured during usual care.; • Incidence of hypoglycemia defined as blood glucose measurement < 4 mmol/l at any time point between start of surgery and end of study. Timepoint(s) of evaluation of this end point: For NGAL, KIM‐1, plasma ketones and incidence of keto‐acidosis:; ; ‐ On day of surgery:; • Before start of surgery (after placement of arterial line); • At time of start of cardiopulmonary bypass (+/‐ 20 min); • At the end of cardiopulmonary bypass (+/‐ 20 min); • At time of transport to ICU (+/‐ 20 min); ‐ Postoperatively; • Measured daily, in the morning between 8:00 and 12:00 until postoperative day 2.; ; For eGFR (creatinine); • Measured daily, in the morning between 8:00 and 12:00 until postoperative day 4.; ; For peak and average glucose and incidence of hypoglycaemia:; • any measurement occurring between start of surgery and end of study until postoperative day 4, as part of routine care. INCLUSION CRITERIA: • 18 to 90 years old (inclusive) • Undergoing elective cardiac surgery with cardio‐pulmonary bypass. • Providing informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60