Dapagliflozin for Cardio-renal Protection After ICU Discharge

NCT07025629 | Recruiting Phase 3

• 1 other identifier: APHP220826
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 2

Brief Summary

Several millions of patients are admitted to ICUs in Europe or USA each year. We and others, have shown that patients discharged from intensive care units (ICU) have a high incidence of cardiovascular and/or renal events and high mortality rate (22%) during the year following ICU discharge. Furthermore, a very recent meta-analysis found an excess hazard of late cardiovascular events which persists for at least 5 years following hospital discharge in sepsis survivors. Hence, many international ICU societies recommended investigating and improving post-ICU outcome with scarce guidance. We demonstrated that the proportion of ICU patients dying or presenting cardiovascular events within the year following ICU discharge is reported \~25% \[2\], reaching \~40% in some studies when considering patients with acute kidney injury (AKI). Plasma biomarkers at ICU discharge have good predictive value and patients with increased kidney or cardiovascular biomarkers display high risk of such events. In addition, we and others demonstrated that AKI or sub-AKI (patient not meeting the AKI definition but with an increased kidney related biomarker) could induce remote cardio-vascular injury and fibrosis, which may be involved in the poor long-term prognosis of ICU-acquired AKI. We hypothesize that strategy that prevent worsening in cardiovascular and/or renal injuries and/or in cardiovascular consequences of sub-AKI and AKI after ICU discharge improve long-term outcomes in ICU survivors. SGLT2 inhibitors are widely recognized as key drugs to protect the kidney and/or the myocardium in chronic diseases such as diabetes or heart failure. Cardio protective effect of SGLT2 inhibitors is optimal in patients with higher cardiac biomarker.

Conditions

Heart Failure and Chronic Kidney Disease Post-ICU

Keywords

Cardiovascular outcomes; Renal outcomes; SGLT2 inhibitors; Cardiorenal syndrome; Critical illness recovery

Outcome Measures

Primary Outcomes (3)

• All-cause mortality

  Within the year after randomization

• Unscheduled hospital hospitalization for heart failure

  All potential hospitalizations for heart failure should be recorded in the eCRF and submitted to adjudication. The Clinical Event Adjudication (CEA) committee members will adjudicate the events as specified in the (CEA) Charter.

  Within the year after randomization

• Decrease of eGFR by more than 50% from ICU discharge and/or end stage kidney disease defined as an eGFR<15ml/min/1.73m² and/or initiation of renal replacement therapy and/or kidney transplantation

  Dialysis, eGFR events (\<15 mL/min/1.73m²; ≥50% decline in eGFR) will be recorded in the eCRF and submitted for adjudication. eGFR baseline is defined as the local laboratory value at inclusion visit. The eGFR will be calculated using CKD-EPI equation without race coefficient \[87, 88\].

  Within the year after randomization

Secondary Outcomes (16)

• Unscheduled hospital hospitalization for acute heart failure

  Within the year after randomization

• Unscheduled hospital hospitalization for stroke

  Within the year after randomization

• Unscheduled hospital hospitalization for acute coronary syndrome

  Within the year after randomization

• Occurrence of severe chronic kidney disease

  Within the year after randomization

• • Decrease of estimated glomerular filtration rate of more than 50% from baseline

  Within the year after randomization

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

One tablet of dapagliflozin 10 mg will be administered once daily from randomization and for 12 months period +/- 15 days..

Drug: Dapagliflozin 10 MG Oral Tablet [Farxiga]

Placebo of dapagliflozin

PLACEBO COMPARATOR

One tablet of placebo of dapagliflozin 10 mg will be administered, per os, once daily from randomization and for 12 months period ± 15 days.

Drug: One tablet of placebo of dapagliflozin 10 mg

Interventions

One tablet of placebo of dapagliflozin 10 mg DRUG

One tablet of placebo of dapagliflozin 10 mg will be administered, per os, once daily from randomization and for 12 months period ± 15 days.

Placebo of dapagliflozin

Dapagliflozin 10 MG Oral Tablet [Farxiga] DRUG

One tablet of dapagliflozin 10 mg will be administered once daily from randomization and for 12 months period +/- 15 days..

Dapagliflozin

Eligibility Criteria

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

You may qualify if:

• Age \>or= 18 years
• Mechanical ventilation and/or vasopressors/inotropes for more than 24h during ICU stay
• Patients ready to be discharged from ICU according to physician in charge
• Inform consent form signed by the patient

You may not qualify if:

• Pregnancy
• Ability to become pregnant and refusal to use effective contraception during all study treatment Women of childbearing potential (WOCBP)\*\* must agree to use adequate contraception according to Recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG).
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation
• oral
• injectable
• implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system ( IUS)
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Hospital Saint Louis

Paris, 75010, France

RECRUITING

Saint Louis Hospital

Paris, 75010, France

NOT YET RECRUITING

Related Publications (8)

• Sano M, Goto S. Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects. Circulation. 2019 Apr 23;139(17):1985-1987. doi: 10.1161/CIRCULATIONAHA.118.038881. No abstract available.

  PMID: 31009585 BACKGROUND

• Chang YK, Choi H, Jeong JY, Na KR, Lee KW, Lim BJ, Choi DE. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury. PLoS One. 2016 Jul 8;11(7):e0158810. doi: 10.1371/journal.pone.0158810. eCollection 2016.

  PMID: 27391020 BACKGROUND

• Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Furtado RHM, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019 Jan 5;393(10166):31-39. doi: 10.1016/S0140-6736(18)32590-X. Epub 2018 Nov 10.

  PMID: 30424892 BACKGROUND

• Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Ofstad AP, Pfarr E, Jamal W, Packer M. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020 Sep 19;396(10254):819-829. doi: 10.1016/S0140-6736(20)31824-9. Epub 2020 Aug 30.

  PMID: 32877652 BACKGROUND

• Depret F, Hollinger A, Cariou A, Deye N, Vieillard-Baron A, Fournier MC, Jaber S, Damoisel C, Lu Q, Monnet X, Rennuit I, Darmon M, Leone M, Guidet B, Sonneville R, Montravers P, Pili-Floury S, Lefrant JY, Duranteau J, Laterre PF, Brechot N, Oueslati H, Cholley B, Struck J, Hartmann O, Mebazaa A, Gayat E, Legrand M. Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients. Am J Respir Crit Care Med. 2020 Sep 15;202(6):822-829. doi: 10.1164/rccm.201910-1950OC.

  PMID: 32516543 BACKGROUND

• Legrand M, Rossignol P. Cardiovascular Consequences of Acute Kidney Injury. N Engl J Med. 2020 Jun 4;382(23):2238-2247. doi: 10.1056/NEJMra1916393. No abstract available.

  PMID: 32492305 BACKGROUND

• Gayat E, Cariou A, Deye N, Vieillard-Baron A, Jaber S, Damoisel C, Lu Q, Monnet X, Rennuit I, Azoulay E, Leone M, Oueslati H, Guidet B, Friedman D, Tesniere A, Sonneville R, Montravers P, Pili-Floury S, Lefrant JY, Duranteau J, Laterre PF, Brechot N, Chevreul K, Michel M, Cholley B, Legrand M, Launay JM, Vicaut E, Singer M, Resche-Rigon M, Mebazaa A. Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study. Crit Care. 2018 Jan 18;22(1):8. doi: 10.1186/s13054-017-1922-8.

  PMID: 29347987 BACKGROUND

• Arrigo M, Feliot E, Gayat E, Mebazaa A. Cardiovascular events after ICU discharge in patients with new-onset atrial fibrillation: A report from the FROG-ICU study. Int J Cardiol. 2018 Nov 1;270:203. doi: 10.1016/j.ijcard.2018.07.080. Epub 2018 Jul 20. No abstract available.

  PMID: 30045823 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Cardio-Renal Syndrome

Interventions

dapagliflozin; Tablets

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; 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

• Alexandre Mebazaa, MD-PHD

  APHP

  PRINCIPAL INVESTIGATOR

• François DEPRET, MD-PHD

  APHP

  STUDY CHAIR

Central Study Contacts

François DEPRET, MD-PHD

CONTACT

0142499570; francois.depret@aphp.fr

Alexandre MEBAZAA, MD-PhD

CONTACT

01 49 95 80 85; alexandre.mebazaa@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Treatments will be conditioned and labelled by the Contract manufacturing organization AGEPS according to a list provided by an independent person and assigning a treatment arm to each treatment number. Randomization and treatment numbers lists are kept strictly confidential until the time of unblinding, and will not be accessible by anyone involved in the study, with the exception of the independent, unblinded statistician approving the randomization scheme; the study will be kept blinded to patients, investigators and study personnel also during the entire study period; The identification of treatment will be concealed by the use of a matching placebo to the study product that will be provided in boxes identical in packaging, labeling and appearance
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two groups of participants will each receive different interventions.One group will receive dapagliflozin for the same amount of time that a second group will receive Placebo of dapagliflozin .

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: June 17, 2025
• Study Start: December 2, 2025
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): January 15, 2029
• Last Updated: February 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: The data will be available one year after publication, for 5 years

Locations

FR (2)