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…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Neutrophil gelatinase-associated lipocalin (NGAL) concentration in plasma,
measured on the morning of postoperative day 2, between 8:00 and 12:00.
Secondary outcome
• 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.
• Ketones in blood.
• 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.
Moments of measurement:
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.
Background summary
Acute kidney injury is one of the most common complications after cardiac
surgery. The new antidiabetic therapy, sodium glucose transport protein 2
inhibitors (SGLT2i) possess renoprotective properties and have been found to
reduce acute kidney injury in large cardiovascular outcome trials in patients
with diabetes mellitus.
Study 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.
Study design
Single-center, open-label, parallel-group, balanced (1:1), stratified (diabetes
mellitus type 2, 50-50), randomized, controlled (usual care), phase IV clinical
trial.
Intervention
The intervention group receives once daily 10 mg empagliflozin starting 7 days
before surgery to be continued until two days postoperatively.
The control group will follow usual perioperative care.
Study burden and risks
General trial-related burden:
For this study, additional blood will be drawn to study the effect of the
intervention. All blood will be drawn concurring with measurements as part of
standard perioperative care. Therefore, no additional venepunctures will occur
as part of this study*the total amount of additional blood drawn: 28 ml.
Intervention group related burden:
Patients in the control group will receive standard perioperative care.
Patients in the intervention group will take 1 tablet of 10 mg empagliflozin
daily from 7 days before surgery until 2 days postoperative (including the day
of surgery). Patients in the intervention group run a risk of side effects
related to the study drug. These are relatively rare. Potential participants
will be informed about the following side effects: genitourinary infections,
euglycaemic ketoacidosis, and hypoglycaemia. There is only a risk of
hypoglycaemia in patients with diabetes mellitus that are already taking other
glucose-lowering drugs.
Regarding potential side-effects:
- genitourinary infections usually occur after longer-term use of SGLT2
inhibitors; in this study, patients will only receive this medication for 10
days. In addition, this side effect's management is straightforward with
antimicrobial treatment.
- hypoglycaemia: only patients with diabetes mellitus are at risk, according to
previous research. These patients will receive an individualised adaptation of
their glucose-lowering medication by the researchers. In addition, blood
glucose will be monitored in all patients according to standard perioperative
cardiac surgery care.
- euglycaemic ketoacidosis: a lowering of the pH in the blood through the
build-up of ketones. This side-effect has been described in patients with
diabetes mellitus and a (relative) insulin deficiency. Patients without
diabetes are not at risk, according to previous research. We will monitor
perioperative glucose and ketone levels in all patients in the study as well as
for the incidence of metabolic acidosis. Should this side-effect occur, we will
treat with a glucose-insulin infusion, thereby inhibiting ketone production.
There is solid evidence to support that SGLT2 inhibitors are renoprotective.
Acute kidney injury is a common complication after cardiac surgery. Our
hypothesis is, therefore, that patients in the intervention group will receive
protection from kidney injury. In addition, the results from this trial could
lead to the improvement of care and protection of patients undergoing cardiac
surgery. The side-effect profile of empagliflozin is mild, and participants
will be intensively monitored in this study. Therefore, we estimate that the
benefits outweigh the risks for participation in this trial.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
• 18 to 90 years old (inclusive)
• Undergoing elective cardiac surgery with cardio-pulmonary bypass.
• Providing informed consent
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.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003172-13-NL |
| CCMO | NL78156.018.21 |
| Other | NL9561 |