E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiac surgery-associated acute kidney injury |
cardio-chirurgie geassocieerde nierinsufficiëntie |
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E.1.1.1 | Medical condition in easily understood language |
Kidney injury occurring after cardiac surgery |
Nier schade die optreed na een hart operatie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080266 |
E.1.2 | Term | Stage 1 acute kidney injury |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
Te onderzoeken of preoperative gestart (7 dagen) en perioperatief gecontinueerd (tot dag 2 na de operatie) empagliflozine 10 mg (dagelijks) de acute nierschade-indicator "neutrophil gelatinase-associated lipocalin" (NGAL) op dag 2 na de operatie kan verminderen in patiënten die cardiochirurgie met een hartlong-machine ondergaan. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
• Te onderzoeken of empagliflozine perioperatieve markers van nierschade kan verminderen in patiënten die cardiochirurgie met een hartlong-machine ondergaan. • Te onderzoeken of empagliflozine kan zorgen voor behoud van nierfunctie (eGFR) in patiënten die cardiochirurgie met een hartlong-machine ondergaan. • Het effect te onderzoeken van empagliflozine op perioperatieve glycemie en de incidentie van hypoglycaemie in patiënten die cardiochirurgie met een hartlong-machine ondergaan. • Het effect te onderzoeken van empagliflozine op perioperatieve ketonemie en de incidentie van ketoacidose in patiënten die cardiochirurgie met een hartlong-machine ondergaan. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 18 to 90 years old (inclusive) • Undergoing elective cardiac surgery with cardio-pulmonary bypass. • Providing informed consent |
• 18 tot 90 jaar oud (inclusief) • Electieve cardio-chirurgie met hartlongmachine. • Afgegeven informed consent |
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E.4 | Principal exclusion criteria |
• Current treatment with SGLT2 inhibitors. • Diabetes Mellitus Type 1 • BMI<25 for people with type 2 diabetes • Reduced renal function at baseline with eGFR < 30 ml/min. • Systolic blood pressure < 100 mmHg at time of inclusion. • Emergency surgery, defined as in need of surgery for medical reasons < 7 days, i.e. “S1-4” according to the Amsterdam UMC classification. • Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods. • Known or suspected allergy to trial products or other drugs in the same class.
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• Huidige behandeling met SGLT2 remmers. • Type 1 Diabetes Mellitus • BMI<25 voor mensen met type 2 diabetes. • Verminderde nierfunctie met eGFR<30 ml/min. • Systolische bloeddruk <100 mmHg op moment van inclusie. • Spoed operatie gedefineerd als operatie genoodzaakt voor medische redenen binnen 7 dagen. (i.e. “S1-4” spoedclassificatie binnen het Amsterdam UMC. • Potentieel vruchtbare vrouwen die mogelijks zwanger zijn, borstvoeding geven of van plan zijn zwanger te worden of geen voorbehoedsmiddelen gebruiken. • Bekende of vermoedde allergie voor een het studiemiddelen of voor een binnen de zelfde medicijnklasse. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Neutrophil gelatinase-associated lipocalin (NGAL) concentration in plasma on postoperative day 2. |
• Neutrophil gelatinase geassocieerd lipocalin (NGAL) concentratie in plasma op postoperatieve dag 2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Measured on morning of postoperative day 2, between 8:00 and 12:00. |
gemeten in de ochtend van postoperatieve dag 2 tussen 8:00 en 12:00 |
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E.5.2 | 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. |
• Neutrophil gelatinase geassocieerd lipocalin (NGAL) concentratie in plasma. • Kidney Injury Molecule-1 (KIM-1) in plasma. • Estimated Glomerular Filtration Rate (eGFR) gebaseerd op creatinine metingen. • Bloed ketonen concentratie. • Incidentie van keto-acidose gedefinieerd als combinatie van bloed ketone concentratie >3mmol/l in combinatie met hoog-anion gap acidose ([Na+]-[Cl-]-[HCO3-]>12) • Piek en gemiddeld bloed glucose concentraties tijdens operatie en in de postoperatieve periode, gemeten als onderdeel van standaard zorg. • Incidentie van hypoglycemie gedefinieerd as bloed glucose concentratie < 4 mmol/l
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E.5.2.1 | 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. |
Voor NGAL, KIM-1, ketonen en incidentie keto-acidose:
Dag van de operatie: • Voor de start van operatie (na plaatsing van arterielijn) • Op moment van start hartlongmachine (+/- 20 min) • Op moment van einde van hartlongmachine (+/- 20 min) • Op moment van transport naar ICU (+/- 20 min)
Postoperatief • Dagelijks gemeten in de ochtend tussen 8:00 en 12:00 dagen tot postoperatieve dag 2.
Voor eGFR (creatinine) • Dagelijks gemeten in de ochtend tussen 8:00 en 12:00 dagen tot postoperatieve dag 4.
Voor piek en gemiddelde glycemie en incidentie van hypoglycemie • op elk gemeten moment tussen start van operatie en einde van de studie postoperatieve dag 4, als onderdeel van routine zorg. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |