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Publications

Journal Article Clinical Trial Protocol Epublish

PubMed: 41991273 DOI: 10.1136/bmjopen-2025-108119

Dapagliflozin for cardiorenal protection after intensive care unit discharge: a protocol for a randomised controlled trial evaluating dapagliflozin at ICU discharge for cardiorenal protection (DAPA-ICU).

BMJ Open 16(4):e108119

Authors: François Dépret, Benjamin Chousterman, Claire Roger, Marc Garnier, Robin Lalande, Thomas Kerforne, Emmanuelle Rouve, Anne-Claire Lukaszewicz, Alexandre Ouattara, Hamid Merdji, Emanuele Turbil, Belaid Bouhemad, Jean-Pierre Quenot, Agathe Delbove, Quentin Levrat, Marion Jully, Stephane Legriel, Wulfran Bougouin, Kada Klouche, Antoine Kimmoun, Pierre Asfar, Eric Vicaut, Alexandre Mebazaa

Affiliations

  • Université Paris Cité, Paris, France.
  • Department of Anesthesiology, Surgical Critical Care and Burn Unit, Assistance Publique - Hopitaux de Paris, Paris, France.
  • INI-CRCT, Nancy, France.
  • Université Paris Cité, INSERM U942 MASCOT, Paris, France.
  • Department of Anesthesia and Critical Care, AP-HP, Hôpital Lariboisière, Paris, France.
  • Division of Anesthesia and Critical Care, Pain and Emergency Medicine, UR-UM103 IMAGINE, University Montpellier, Nîmes University Hospital, Nimes, France.
  • Department of Anesthesiology and Critical Care, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
  • Medico-Surgical Intensive Care Unit, CHU Clermont-Ferrand, Clermont-Ferrand, France.
  • Department of Anesthesiology and Critical Care, CHU de Poitiers, Poitiers, France.
  • Critical Care Unit, CH Perpignan, Perpignan, France.
  • Department of Anesthesiology and Critical Care, Hospices Civils de Lyon, Lyon, France.
  • Department of Cardiovascular Anesthesia and Critical Care, CHU Bordeaux, University Hospital of Bordeaux, INSERM, Biologie des maladies cardiovasculaires, Bordeaux, France.
  • Medical Critical Care, CHU de Strasbourg, Strasbourg, France.
  • Critical Care Unit, CH Aurillac, Aurillac, France.
  • Centre Hospitalier Universitaire de Dijon Pole Anesthesie Reanimations Chirurgicales Urgences et Medecine legale, Dijon, France.
  • Université Bourgogne-Europe, INSERM, CTM 1231, Equipe Lipness, Service de Médecine Intensive-Réanimation, Dijon, France.
  • Réanimation Polyvalente, Centre Hospitalier Bretagne Atlantique, Vannes, France.
  • Critical Care Unit, CH La Rochelle, La Rochelle, France.
  • Critical Care Unit, CH d Antibes Juan les Pins, Antibes, France.
  • Intensive Care Unit, Centre Hospitalier de Versailles, Le Chesnay, France.
  • Medico-Surgical Critical Care, Hôpital Privé Jacques Cartier, Massy, France.
  • Intensive Care, Universite de Montpellier, Montpellier, France.
  • Medical Critical Care, CHRU Nancy, Nancy, France.
  • Medical Critical Care, CHU Angers, Angers, France.
  • Univeristé Paris Cité, INSERM U942 MSCOT, Paris, France.
  • Unité de recherche Clinique, Lariboisière, Saint-Louis, Fernand Widal, Paris, France.
  • Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, Paris, France.

Abstract

INTRODUCTION

Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors.

METHOD AND ANALYSIS

This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres.

ETHICS AND DISSEMINATION

This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis.

TRIAL REGISTRATION NUMBER

NCT07025629.

MeSH

Mortality, Teaching, Heart Failure, Heart, Biomarkers, Intensive Care Units