proMoting Effective Renoprotection in Cardiac sURgery Patients by Inhibition of SGLT-2

NCT05590143 | Active Not Recruiting Phase 4 DMC FDA Drug

• 6 other identifiers: MERCURI-22022-002453-252024-515260-31-0010140022010003NL81190.018.222022.0795
• Study Type: interventional
• Target: 784
• Locations: 1 country
• Sites: 6

Brief Summary

Multi-centre, triple-blinded (patients, physicians, investigators), parallel-group, balanced (1:1), stratified (sex, type 2 diabetes mellitus), randomized, controlled (placebo), phase IV clinical trial to investigate the potential of preoperative initiation (from day 1 before surgery) 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 (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) in adult (\>18 years old) patients undergoing cardiopulmonary bypass surgery.

Conditions

Acute Kidney Injury; Cardiac Surgery; Sodium-Glucose Transporter 2 Inhibitor

Keywords

Cardiac Surgery; Acute Kidney Injury; SGLT2i; Dapagliflozin

Outcome Measures

Primary Outcomes (1)

• AKI

  Incidence of Acute Kidney Injury (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.

  Recorded daily until day 7 postoperatively or until discharge from hospital (earlier).

Secondary Outcomes (22)

• AKI-3

  Recorded daily until day 7 postoperatively or until discharge from hospital (earlier).

• eGFR

  Recorded daily until day 7 postoperatively or until discharge from hospital (earlier).

• AF

  Recorded daily until day 7 postoperatively or until discharge from hospital (earlier).

• LoS-ICU

  Recorded on day of discharge from ICU, assessed up to 30 days.

• LoS-Hos

  Recorded on day of discharge from the hospital, assessed up to 30 days.

Study Arms (2)

Intervention

EXPERIMENTAL

Dapagliflozin 10 mg

Drug: Dapagliflozin 10 MG Oral Tablet [Farxiga]

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

Dapagliflozin 10 MG Oral Tablet [Farxiga] DRUG

One oral tablet, once daily starting one day prior to surgery and continued until two days postoperatively (four doses).

Also known as: Farxiga, SGLT2i, Sodium glucose co-transporter-2 inhibitor

Intervention

Placebo DRUG

One oral tablet, once daily starting one day prior to surgery and continued until two days postoperatively (four doses).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 years-old
• Undergoing elective cardiac surgery.
• Providing informed consent

You may not qualify if:

• Current treatment with SGLT2 inhibitors
• Diabetes Mellitus Type 1
• History of diabetic keto acidosis
• 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)
• 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

Sponsors & Collaborators

• Amsterdam UMC: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (6)

OLVG

Amsterdam, 1090 HM, Netherlands

Location

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

Amphia Hospital

Breda, 4818 CK, Netherlands

Location

Medisch Spectrum Twente

Enschede, 7500 KA, Netherlands

Location

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

St Antonius Hospital

Nieuwegein, 3430 EM, Netherlands

Location

Related Publications (8)

• Semler MW, Rice TW, Shaw AD, Siew ED, Self WH, Kumar AB, Byrne DW, Ehrenfeld JM, Wanderer JP. Identification of Major Adverse Kidney Events Within the Electronic Health Record. J Med Syst. 2016 Jul;40(7):167. doi: 10.1007/s10916-016-0528-z. Epub 2016 May 27.

  PMID: 27234478 BACKGROUND

• Myles PS, Shulman MA, Heritier S, Wallace S, McIlroy DR, McCluskey S, Sillar I, Forbes A. Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia. BMJ Open. 2017 Aug 18;7(8):e015828. doi: 10.1136/bmjopen-2017-015828.

  PMID: 28821518 BACKGROUND

• Federici S, Bracalenti M, Meloni F, Luciano JV. World Health Organization disability assessment schedule 2.0: An international systematic review. Disabil Rehabil. 2017 Nov;39(23):2347-2380. doi: 10.1080/09638288.2016.1223177. Epub 2016 Nov 7.

  PMID: 27820966 BACKGROUND

• Stolk E, Ludwig K, Rand K, van Hout B, Ramos-Goni JM. Overview, Update, and Lessons Learned From the International EQ-5D-5L Valuation Work: Version 2 of the EQ-5D-5L Valuation Protocol. Value Health. 2019 Jan;22(1):23-30. doi: 10.1016/j.jval.2018.05.010. Epub 2019 Jan 2.

  PMID: 30661630 BACKGROUND

• Lau D, Pannu N, James MT, Hemmelgarn BR, Kieser TM, Meyer SR, Klarenbach S. Costs and consequences of acute kidney injury after cardiac surgery: A cohort study. J Thorac Cardiovasc Surg. 2021 Sep;162(3):880-887. doi: 10.1016/j.jtcvs.2020.01.101. Epub 2020 Mar 3.

  PMID: 32299694 BACKGROUND

• Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. PLoS Med. 2019 Dec 9;16(12):e1002983. doi: 10.1371/journal.pmed.1002983. eCollection 2019 Dec.

  PMID: 31815931 BACKGROUND

• Gilbert RE, Thorpe KE. Acute kidney injury with sodium-glucose co-transporter-2 inhibitors: A meta-analysis of cardiovascular outcome trials. Diabetes Obes Metab. 2019 Aug;21(8):1996-2000. doi: 10.1111/dom.13754. Epub 2019 May 24.

  PMID: 31050116 BACKGROUND

• Oosterom-Eijmael M, Monteiro de Oliveira NP, Niesten ED, Tolsma M, Snellen FT, Gerritse BM, Scohy TV, Rettig T, Godfried MB, Voogd MF, Wink J, van der Werff LM, Eberl S, Preckel B, Hermanides J, van Raalte DH, Hulst AH; MERCURI-2 study group. Study protocol of the multicentre, randomised, triple-blind, placebo-controlled MERCURI-2 trial: promoting effective renoprotection in cardiac surgery patients by inhibition of sodium glucose cotransporter (SGLT)-2. BMJ Open. 2025 May 16;15(5):e095504. doi: 10.1136/bmjopen-2024-095504.

  PMID: 40379310 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

dapagliflozin; Tablets

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Daniël H. van Raalte, MD, PhD

  Internal Medicine Specialist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 21, 2022
• Study Start: June 9, 2023
• Primary Completion: May 14, 2025
• Study Completion: September 1, 2025
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 1 year after peer-reviewed publication of the primary trail results.
• Access Criteria: Official request made to the principal investigator.

Locations

NL (6)