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

Intervention / Treatment

• Drug: Dapagliflozin 10 MG Oral Tablet [Farxiga]
• Drug: One tablet of placebo of dapagliflozin 10 mg

Primary Outcome Measures

• All-cause mortality (Within the year after randomization)
• Unscheduled hospital hospitalization for heart failure (Within the year after randomization)
  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.
• 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 (Within the year after randomization)
  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 \[87, 88\].

Countries

France

Locations and Investigators

• Hospital Saint Louis, Paris, France (Recruiting)
  • François DEPRET, MD-PhD
• Saint Louis Hospital, Paris, France (Not yet recruiting)
  • François DEPRET, MD-PHD
  • Alexandre Mebazaa, MD-PhD

Study Officials

• Alexandre Mebazaa, MD-PHD (Principal Investigator) — APHP
• François DEPRET, MD-PHD (Study Chair) — APHP