DAPAGLIFLOZIN for Acute kidney injury (AKI) | Reduced estimated glomerular filtration rate (reduced eGFR) | Elevated NT-proBNP (cardiac biomarker)

Inclusion criteria

• {"criterion_text":"- Age >or= 18 years\n- Mechanical ventilation and/or vasopressors/inotropes for more than 24h during ICU\n- Patients ready to be discharged from ICU according to physician in charge\n- Inform consent form signed by the patient\n- NT-proBNP greater than 800 ng/L and/or Estimated glomerular filtration rate (eGFR) between 25ml/min/1.73m² and 90ml/min/1.73m² of body-surface area (CKD-EPI formula) at inclusion"}

Exclusion criteria

• {"criterion_text":"- Pregnancy or Breast feeding or Ability to become pregnant and refusal to use effective contraception during all study treatment\n- Known hypersensitivity to dapagliflozin or any of the excipients\n- Patients treated with dapagliflozin before ICU admission\n- Patients with severe cirrhosis (Child-Pugh C)\n- Estimated glomerular filtration rate (eGFR) below 25 ml per minute per 1.73 m2 of body-surface area (CKD -EPI formula).\n- Patient for whom treatment with Dapagliflozine is strongly recommended according to recent international guidelines: •\tpatients with type 2 diabetes mellitus adults for whom the treatment is inadequately controlled as an adjunct to diet and exercise: either as monotherapy when metformin is considered inappropriate due to inadequate tolerance, or in addition to other medications for the treatment of type 2 diabetes, •\tsymptomatic chronic heart failure with reduced or preserved left ventricular ejection fraction, •\tchronic kidney disease, in addition to standard therapy with a glomerular filtration rate (GFR) between 25 and 75 mL/min/1.73m² and a urinary albumin-to-creatinine ratio (ACR) between 200 and 5000 mg/g and treated for at least 4 weeks with an ACE inhibitor or angiotensin 2 receptor blocker (ARB II or sartan).\n- Patient without national health insurance, and patient on AME (state medical aid)\n- Persons deprived of liberty by a judicial or administrative decision\n- Participation in other interventional study"}

Primary endpoints

• {"endpoint_text":"- A composite outcome composed of: •\tall-cause mortality, at one year after ICU discharge •\tand/or unscheduled hospital hospitalization for heart failure, at one year after ICU discharge •\tand/or a decrease of eGFR by more than 50% from baseline (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 at one year after ICU discharge","definition_or_measurement_approach":"Composite measured at one year after ICU discharge including: all-cause mortality at one year; unscheduled hospitalisation for heart failure at one year; and/or renal outcome defined as >50% decrease in eGFR from baseline (ICU discharge) and/or end-stage kidney disease (eGFR <15 ml/min/1.73m²) and/or initiation of renal replacement therapy and/or kidney transplantation at one year."}

Secondary endpoints

• {"endpoint_text":"- Unscheduled hospital hospitalization for cardiovascular events (acute heart failure, stroke, acute coronary syndrome) during the year following ICU discharge","definition_or_measurement_approach":"Unscheduled hospitalisation for specified cardiovascular events during the year after ICU discharge."}
• {"endpoint_text":"- Occurrence of severe chronic kidney disease one year after ICU discharge defined as eGFR <30 ml/min/1.73m2","definition_or_measurement_approach":"Presence of severe chronic kidney disease at one year defined by eGFR <30 ml/min/1.73m²."}
• {"endpoint_text":"- Decrease of estimated glomerular filtration rate of more than 50% from baseline one year after ICU discharge","definition_or_measurement_approach":"Decrease in eGFR >50% from baseline (ICU discharge) assessed at one year."}
• {"endpoint_text":"- New episode of acute kidney injury (according to the KDIGO criteria) requiring hospitalization in the year following ICU discharge","definition_or_measurement_approach":"New AKI episode per KDIGO criteria requiring hospitalisation within one year after ICU discharge."}
• {"endpoint_text":"- Occurrence of end stage kidney disease defined (eGFR<15ml/min/1.73m2) and/or initiation of renal replacement therapy and/or kidney transplantation one year after ICU discharge","definition_or_measurement_approach":"Occurrence of ESRD (eGFR <15 ml/min/1.73m²) and/or initiation of RRT and/or kidney transplant within one year."}
• {"endpoint_text":"- Variation of NT-proBNP or BNP, eGFR between 12 months (end of treatment) and 12 months + 6 weeks (end of study)","definition_or_measurement_approach":"Change in NT-proBNP/BNP and eGFR between end of treatment (12 months) and end of study (12 months + 6 weeks)."}
• {"endpoint_text":"- Occurrence of cardiovascular events during of the treatment duration","definition_or_measurement_approach":"Cardiovascular events occurring during the treatment period."}
• {"endpoint_text":"- Occurrence of renal events during of the treatment duration","definition_or_measurement_approach":"Renal events occurring during the treatment period."}
• {"endpoint_text":"- Occurrence of global outcome events during of the treatment duration","definition_or_measurement_approach":"Global outcome events occurring during the treatment period."}
• {"endpoint_text":"- Safety endpoints are evaluated during the year after ICU discharge: Urinary tract infection / Necrotizing fasciitis / Symptomatic Diabetic ketoacidosis (Arterial pH <7.3 and Ketone-positive urine and Anion gap <10 mEq/L and Drowsy, stupor or coma) / Major hypoglycaemia (glycemia < 3mmol/L) /\tDeath of any cause","definition_or_measurement_approach":"Safety outcomes assessed during the year after ICU discharge including specified infections, necrotizing fasciitis, symptomatic diabetic ketoacidosis (criteria provided), major hypoglycaemia (<3 mmol/L), and all-cause death."}

France

Earliest CTIS Part Ii Submission Date

17-01-2025

Latest Decision Or Authorization Date

07-05-2025

Processing Time Days

110

Number Of Sites

16

Number Of Participants

600

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France