This study has been transitioned to CTIS with ID 2024-515260-31-00 check the CTIS register for the current data. To investigate the potential of preoperative initiation and perioperative continuation until day 2 after surgery of the SGLT2 inhibitor…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of AKI occurring in 7 days after surgery, according to KDIGO
criteria, defined as an increase in serum creatinine by 0.3 mg/dl (26.5 mmol/l)
within 48 hours; or an increase in serum creatinine to 1.5 times baseline,
within 7 days; or a urine output <0.5 ml/kg/h for >6 hours.
Secondary outcome
1. Incidence of Stage 3 AKI according to KDIGO criteria, measured until day 7
postoperatively. 2. Postoperative change of eGFR compared to the baseline eGFR,
measured daily until day 7 postoperatively. 3. De novo postoperative atrial
fibrillation, registered on a 12-lead ECG. 4. Length of Stay in the Intensive
Care Unit, measured in days. 5. Length of Stay in hospital, measured in days.
6. MAKE: Major Adverse Kidney Events, within 30 postoperative days. Composite
endpoint of death, new dialysis, and worsened renal function.1 7. MACE: Major
Adverse Cardiovascular Events, within 30 postoperative days. Composite endpoint
of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal
ischaemic cerebral vascular accident (iCVA) and hospitalization for heart
failure. 8. Patient reported quality of recovery measured at day 30
postoperatively, according to the following three questionnaires: o DAH30: Days
at Home in first 30 days2 o WHO-DAS 2.0: World Health Organisation Disability
Assessment Schedule 2.03 o EQ5D5L: 5 level EuroQol 5D questionnaire: a
standardised measure of health status developed by the EuroQol Group to provide
a simple, generic measure of health for clinical and economic appraisal 4 9.
Safety outcomes: genital mycotic infections, diabetic keto-acidosis, and
hypoglycaemia, in addition to incidence of postoperative complications and
Serious Adverse Events (SAEs). 10. Healthcare and productivity costs will be
objectified to weigh cost-effectiveness, using the following two
questionnaires: o iPCQ: IMTA (Institute for Medical Technology Assessment)
Productivity Cost Questionnaire. o IMCQ: IMTA (Institute for Medical Technology
Assessment) Medical Consumption Questionnaire. 11. Peri-operative glucose
measurements until day 3 postoperatively (routinely measured in clinical
setting): average daily glucose, incidence of hypoglycaemia (blood glucose < 4
mmol/l) and hyperglycaemia (blood glucose > 10 mmol/l) 12. Peri-operative
hemodynamic vital signs on day of surgery and during ICU admission (routinely
measured in clinical setting). 13. Postoperative cardiac function
(echocardiography and cardiac biomarkers) routinely carried out in clinical
practice.14. In the AMC subpopulation, the urine oxygenation (during the days
that a urinary catheter is placed), the correlation between urine oxygenation
and current AKI markers and frequency and duration of measurement interruptions
Background summary
Acute kidney injury is one of the most common complications after cardiac
surgery. The new glucose-lowering therapy, sodium glucose transport protein 2
inhibitors (SGLT2i) possess renoprotective properties in people with chronic
kidney disease in the presence or absence of type 2 diabetes. Large
cardiovascular outcome trials in patients with diabetes observed a lower
incidence of acute kidney injury. However, these studies were not powered to
investigate this nor did acute kidney injury concern an adjudicated endpoint.
Study objective
This study has been transitioned to CTIS with ID 2024-515260-31-00 check the CTIS register for the current data.
To investigate the potential of preoperative initiation and perioperative
continuation until day 2 after surgery of the SGLT2 inhibitor dapagliflozin 10
mg once daily to prevent AKI according to the KDIGO criteria in patients
undergoing cardiopulmonary bypass surgery.
Study design
Multi-centre, triple-blinded (patients, physicians, investigators),
parallel-group, balanced (1:1), stratified (male-female 50-50), randomized,
controlled (placebo), phase IV clinical trial.
Intervention
Participants receive 10 mg dapagliflozin once daily or matching placebo
starting 1 day prior to surgery and continued until two days postoperatively
(four doses).
Study burden and risks
General trial-related burden: We will withdraw 4.5 mL of blood at one day
before surgery and one day postoperatively for biomarker analysis. No extra
venepunctures are required, as these measurements coincide with routine
clinical care. Intervention group related burden: Participants will be asked to
take either 1 tablet of 10 mg dapagliflozin once daily from 7 days before
surgery until 2 days postoperative (including the day of surgery) or a matching
placebo regimen. Patients randomized to dapagliflozin will run a small a risk
of treatable side effects related to the study drug. These are rare for
short-term treatments. Participants will be informed about the following side
effects: 1. Genital mycotic infections: these usually only occur after
longer-term use of SGLT2 inhibitors. In this study, patients will only receive
this medication for up to 10 doses. Treatment of this side effect is
straightforward with antifungal treatment. 2. Euglycemic ketoacidosis: a
lowering of the pH in the blood through the build-up of ketones. This has been
described in patients on long-term treatment and is ascribed to altered insulin
sensitivity through increased glucose loss by SGLT2 inhibition. For this and
other reasons, patients with type 1 diabetes mellitus and patients with type 2
diabetes mellitus and a body-mass-index <25 kg/m2 are excluded from this trail.
We will monitor perioperative glucose and pH levels in all participants
according to routine perioperative care. In addition, patients using insulin
therapy will receive a perioperative glucose/insulin infusion, which suppresses
the ketone production. Should keto acidosis occur in any other patient,
treatment is straightforward with a glucose-insulin infusion. 3. Hypoglycemia:
only patients with diabetes mellitus using sulfonylurea or insulin are at risk,
according to previous research. To prevent this side effect: patients will
receive an individualized adaptation of their glucose-lowering medication by
investigator team. To treat this side-effect, blood glucose will be monitored
in all patients according to standard perioperative cardiac surgery care and
hypoglycaemia treatment protocols with urgent administration of intravenous
glucose are in place. Risk-benefit: There is solid evidence to support that
SGLT2 inhibitors offer kidney protection. Acute kidney injury is a common
complication after cardiac surgery. Our hypothesis is therefore, that patients
in the intervention group will receive protection against acute kidney injury.
In addition, the results from this trial could lead to the improvement of care
and protection of future patients undergoing cardiac surgery. The side-effect
profile of dapagliflozin 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
1. >18 years old 2. Undergoing elective cardiac surgery. 3. Providing informed
consent
Exclusion criteria
1. Current treatment with SGLT2 inhibitors 2. Reduced kidney function at
baseline with eGFR < 20 ml/min at time of inclusion 3. Diabetes Mellitus Type 1
4. History of diabetic keto acidosis 5. Diabetes Mellitus Type 2 with BMI<25
for people with type 2 diabetes who are using multiple daily insulin injections
(both short and long-acting insulin) 6. Systolic blood pressure < 100 mmHg at
time of inclusion 7. Emergency surgery, defined as in need of surgery for
medical reasons < 7 days, i.e. *S1-4* according to the Amsterdam UMC
classification 8. Female of child-bearing potential who is pregnant,
breast-feeding or intend to become pregnant or is not using adequate
contraceptive methods 9. 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
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515260-31-00 |
| EudraCT | EUCTR2022-002453-25-NL |
| ClinicalTrials.gov | NCT05590143 |
| CCMO | NL81190.018.22 |