Dapagliflozine for cardio-renal protection at ICU discharge

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

2 Dec 2025 → ongoing

Decision date (initial)

2025-05-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministry of Health (PHRC N 2021)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the benefit of Dapagliflozin on cardiovascular, renal and global outcome one year after ICU discharge in patients with increased cardiac and/or kidney biomarkers at ICU discharge.

Secondary objectives 6

1. To evaluate the impact of dapagliflozin on renal outcome at one year after ICU discharge
2. To evaluate the impact of dapagliflozin on mortality at one year after ICU discharge
3. To evaluate the impact of dapagliflozin on new hospitalizations for major cardiovascular events at one year after ICU discharge
4. To evaluate the impact of dapagliflozin initiation on potential side effect of the treatment (safety) at one year after ICU discharge
5. To evaluate the possible biological remnant effect of the treatment between 12 months (end of treatment) and 12months + 6 weeks (end of study).
6. To evaluate the benefit of Dapagliflozin on cardiovascular, renal and global outcome depending on treatment duration

Conditions and MedDRA coding

Adult patients discharged alive from ICU with a decreased eGFR, and/or an AKI during ICU stay and/or an elevated NT-proBNP at discharge.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age >or= 18 years
2. Mechanical ventilation and/or vasopressors/inotropes for more than 24h during ICU
3. Patients ready to be discharged from ICU according to physician in charge
4. Inform consent form signed by the patient
5. 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 9

1. Pregnancy or Breast feeding or Ability to become pregnant and refusal to use effective contraception during all study treatment
2. Known hypersensitivity to dapagliflozin or any of the excipients
3. Patients treated with dapagliflozin before ICU admission
4. Patients with severe cirrhosis (Child-Pugh C)
5. Estimated glomerular filtration rate (eGFR) below 25 ml per minute per 1.73 m2 of body-surface area (CKD -EPI formula).
6. 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).
7. Patient without national health insurance, and patient on AME (state medical aid)
8. Persons deprived of liberty by a judicial or administrative decision
9. Participation in other interventional study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A composite outcome composed of: • all-cause mortality, at one year after ICU discharge • and/or unscheduled hospital hospitalization for heart failure, at one year after ICU discharge • and/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

Secondary endpoints 10

1. Unscheduled hospital hospitalization for cardiovascular events (acute heart failure, stroke, acute coronary syndrome) during the year following ICU discharge
2. Occurrence of severe chronic kidney disease one year after ICU discharge defined as eGFR <30 ml/min/1.73m2
3. Decrease of estimated glomerular filtration rate of more than 50% from baseline one year after ICU discharge
4. New episode of acute kidney injury (according to the KDIGO criteria) requiring hospitalization in the year following ICU discharge
5. 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
6. Variation of NT-proBNP or BNP, eGFR between 12 months (end of treatment) and 12 months + 6 weeks (end of study)
7. Occurrence of cardiovascular events during of the treatment duration
8. Occurrence of renal events during of the treatment duration
9. Occurrence of global outcome events during of the treatment duration
10. 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) / Death of any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

François DEPRET

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

François DEPRET

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications