{
  "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.",
  "authors": [
    {
      "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"
      ],
      "name": "François Dépret"
    },
    {
      "affiliations": [
        "INI-CRCT, Nancy, France",
        "Université Paris Cité, INSERM U942 MASCOT, Paris, France",
        "Department of Anesthesia and Critical Care, AP-HP, Hôpital Lariboisière, Paris, France"
      ],
      "name": "Benjamin Chousterman"
    },
    {
      "affiliations": [
        "Division of Anesthesia and Critical Care, Pain and Emergency Medicine, UR-UM103 IMAGINE, University Montpellier, Nîmes University Hospital, Nimes, France"
      ],
      "name": "Claire Roger"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Critical Care, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Marc Garnier"
    },
    {
      "affiliations": [
        "Medico-Surgical Intensive Care Unit, CHU Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Robin Lalande"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Critical Care, CHU de Poitiers, Poitiers, France"
      ],
      "name": "Thomas Kerforne"
    },
    {
      "affiliations": [
        "Critical Care Unit, CH Perpignan, Perpignan, France"
      ],
      "name": "Emmanuelle Rouve"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Critical Care, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Anne-Claire Lukaszewicz"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Anesthesia and Critical Care, CHU Bordeaux, University Hospital of Bordeaux, INSERM, Biologie des maladies cardiovasculaires, Bordeaux, France"
      ],
      "name": "Alexandre Ouattara"
    },
    {
      "affiliations": [
        "Medical Critical Care, CHU de Strasbourg, Strasbourg, France"
      ],
      "name": "Hamid Merdji"
    },
    {
      "affiliations": [
        "Critical Care Unit, CH Aurillac, Aurillac, France"
      ],
      "name": "Emanuele Turbil"
    },
    {
      "affiliations": [
        "Centre Hospitalier Universitaire de Dijon Pole Anesthesie Reanimations Chirurgicales Urgences et Medecine legale, Dijon, France"
      ],
      "name": "Belaid Bouhemad"
    },
    {
      "affiliations": [
        "Université Bourgogne-Europe, INSERM, CTM 1231, Equipe Lipness, Service de Médecine Intensive-Réanimation, Dijon, France"
      ],
      "name": "Jean-Pierre Quenot"
    },
    {
      "affiliations": [
        "Réanimation Polyvalente, Centre Hospitalier Bretagne Atlantique, Vannes, France"
      ],
      "name": "Agathe Delbove"
    },
    {
      "affiliations": [
        "Critical Care Unit, CH La Rochelle, La Rochelle, France"
      ],
      "name": "Quentin Levrat"
    },
    {
      "affiliations": [
        "Critical Care Unit, CH d Antibes Juan les Pins, Antibes, France"
      ],
      "name": "Marion Jully"
    },
    {
      "affiliations": [
        "Intensive Care Unit, Centre Hospitalier de Versailles, Le Chesnay, France"
      ],
      "name": "Stephane Legriel"
    },
    {
      "affiliations": [
        "Medico-Surgical Critical Care, Hôpital Privé Jacques Cartier, Massy, France"
      ],
      "name": "Wulfran Bougouin"
    },
    {
      "affiliations": [
        "Intensive Care, Universite de Montpellier, Montpellier, France"
      ],
      "name": "Kada Klouche"
    },
    {
      "affiliations": [
        "Medical Critical Care, CHRU Nancy, Nancy, France"
      ],
      "name": "Antoine Kimmoun"
    },
    {
      "affiliations": [
        "Medical Critical Care, CHU Angers, Angers, France"
      ],
      "name": "Pierre Asfar"
    },
    {
      "affiliations": [
        "Univeristé Paris Cité, INSERM U942 MSCOT, Paris, France",
        "Unité de recherche Clinique, Lariboisière, Saint-Louis, Fernand Widal, Paris, France"
      ],
      "name": "Eric Vicaut"
    },
    {
      "affiliations": [
        "Université Paris Cité, INSERM U942 MASCOT, Paris, France",
        "Department of Anesthesia and Critical Care, AP-HP, Hôpital Lariboisière, Paris, France",
        "Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis – Lariboisière, Paris, France"
      ],
      "name": "Alexandre Mebazaa"
    }
  ],
  "title": "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)",
  "uid": "623a2172-c58d-575a-a4d5-9a26361ee97f"
}