Dapagliflozin for Cardio-renal Protection After ICU Discharge

Prior treatment

• sexual abstinence
  • The above mentioned risk mitigation measures (contraception) should be maintained during treatment and until the end of relevant systemic exposure.
  • \*\* a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  • A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
  • A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Patients treated with dapagliflozin before ICU admission

Other illness

• Known hypersensitivity to dapagliflozin or any of the excipients
• Patients who admitted or who developed during their ICU stay a urinary tract infection or a perineal infection and patients at risk of skin infection near the perineum (e.g., a sacral pressure ulcer)

Lab values

• Estimated glomerular filtration rate (eGFR) below 25 ml per minute per 1.73 m2 of body-surface area (CKD -EPI formula).
• Patient for whom treatment with Dapagliflozine is strongly recommended according to recent international guidelines:
  • patients 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,
  • symptomatic chronic heart failure with reduced or preserved left ventricular ejection fraction,
  • chronic 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).

Other

• 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).
  • The inclusion of WOCBP requires use of a highly effective contraceptive measure :
• 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
• Breast feeding
• Patients with severe cirrhosis (Child-Pugh C)
• Patient without national health insurance, and patient on AME (state medical aid)
• Persons deprived of liberty by a judicial or administrative decision
• Participation in other interventional study

• 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
• NT-proBNP greater than 800 ng/L or BNP \> 90 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.