Metabolic and Renal Outcomes in Cardiac Surgery Patients Receiving SGLT2 Inhibitors (MERCURI)

The Perioperative Renal and Metabolic Outcomes After Sodium Glucose Cotransporter 2 Inhibitor in Cardiac Surgery - an Open-label Phase IV Randomized Controlled Trial

To investigate the potential of preoperative initiation (3 days) and perioperative continuation (until day 2 after surgery) of empagliflozin(sodium glucose co transporter 2 inhibitor(SGLT-2i)) 10 mg daily to reduce the acute kidney injury marker neutrophil gelatinase-associated lipocalin (NGAL) measured in serum and urine on day 2 postoperatively in patients undergoing cardiopulmonary bypass surgery by comparing a study medication group to a control group in an open-label set-up.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Empagliflozin 10 MG

Detailed Description

Adult patients scheduled for elective cardiopulmonary bypass assisted cardiothoracic surgery will be informed about the study and after receiving informed consent will be divided between two groups in an openlabel fashion:

Intevention group: Takes study medication(10mg Empagliflozin once a day in the morning) 3 days prior to surgery, day of surgery and 2 days post-surgery.

Control group: follows the usual standard of care. At time moment before surgery and before medication is taken blood and urine sample is taken. This is repeated on day of surgery, and the consecutive 2 days after surgery.

Form these samples biomakers for kidney injury will be measured and compared between groups.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam-Zuidoost, Noord-Holland, Netherlands, 1105 AZ
      • Amsterdam University Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Controlled (usual care); Standard of care, Some additional blood drawn and urine collected to compare between both groups
Experimental: Intervention(Medication group); Patients receive 10mg Empagliflozin(SLGT-2i) daily from 3 days prior to surgery untill 2 days post-surgery which includes day of surgery.	Drug: Empagliflozin 10 MG; Patients receive 10mg Empagliflozin(SLGT-2i) daily from 3 days prior to surgery untill 2 days post-surgery which includes day of surgery.; Other Names: Gliflozin; SGLT-2i

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NGAL	Neutrophil gelatinase-associated lipocalin (NGAL) concentration in plasma on postoperative day 2	Day 2 post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil gelatinase-associated lipocalin (NGAL) concentration in plasma.	NGAL measured in plasma	Before surgery, day of surgery, day 1+2 after surgery
Kidney Injury Molecule-1 (KIM-1) in plasma.	KIM-1 concentration measured in plasma	Before surgery, day of surgery, day 1+2 after surgery
Perioperative peak and average blood glucose levels, as measured during usual care.	Glucose levels recorded during usual routine care	During study per untill 4 days post-operatively
Blood ketone levels.	Blood ketones measured intra-operatively	During surgery at 4 measurement moments or during usual care.
Renal functioning (KDIGO criteria)	development of serum creatinine levels and urine output measured untill post-operative day 4	During study period untill post-operative day 4

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ketoacidosis	Incidence of keto-acidosis defined as combination of blood ketone concentration >3mmol/l in combination with high-anion gap acidosis ([Na+]-[Cl-]-[HCO3-]>12).	During study period untill post-operative day 4
Hypoglycemia	Incidence of Hypoglycemia during study period	During study period untill post-operative day 4

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: European Commission
• Investigators: Principal Investigator: Jeroen Hermanides, Dr., Amsterdam University Medical Centre

Publications and helpful links

Helpful Links

• Link of the former published study protocol, National register of the Netherlands has ceased to exist.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): May 26, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: February 8, 2025
• First Submitted That Met QC Criteria: February 8, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 8, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Cardiac surgery; CSA-AKI; SGLT-2i
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: NL78156.018.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Protocol
• IPD Sharing Time Frame: at least 5 years after publication
• IPD Sharing Access Criteria: Relevant reason to validate the request for access of this data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No