{
  "abstract": "Introduction Impairment of the hypothalamic–pituitary–adrenal axis during critical illness, called Critical Illness-Related Corticosteroid Insufficiency (CIRCI), is frequent. There is no standard treatment for CIRCI. This trial aims to determine whether, through biomarker enrichment using CIRCI criteria, hydrocortisone and fludrocortisone, compared with placebo, improve organ dysfunction-free survival in critically ill patients.Methods and analysis French multicentre, placebo-controlled, double-blind superiority trial that will randomly assign adults with CIRCI to receive a 7-day course of hydrocortisone and fludrocortisone or their placebo. Randomisation (1:1) will be stratified by centre and presence or absence of acute respiratory distress syndrome. The primary outcome, number of ventilator-free and vasopressor-free days within 30 days (deaths assigned zero days) after randomisation, will be analysed using a Bayesian model. Patients who do not suffer from CIRCI will be followed up for 90 days.Ethics and dissemination The protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Ouest I, France no 2021T1-11) on 23 September 2021. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals.Trial registration number NCT04404400.",
  "authors": [
    {
      "affiliations": [
        "Department of Intensive Care, APHP University Versailles Saint Quentin-University Paris Saclay, Hopital Raymond-Poincare, Garches, France",
        "Institut Hospitalo Universitaire IHU-3 SEPSIS Institute, Garches, France",
        "Laboratory of Infection & Inflammation-U1173, School of Medicine, INSERM, University Versailles Saint Quentin-University Paris Saclay, Garches, France"
      ],
      "name": "Nicholas Heming"
    },
    {
      "affiliations": [
        "Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care, Pitié-Salpêtrière Hospital, Paris, France"
      ],
      "name": "Elodie Baron"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire (CHU) d’Orléans, Orleans, France",
        "LI²RSO, Université d’Orléans, Château de la Source, Orléans, France"
      ],
      "name": "Grégoire Muller"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Hôpital Nord Franche-Comté - Site de Belfort, Belfort, France"
      ],
      "name": "Julio Badie"
    },
    {
      "affiliations": [
        "U1167 - RID-AGE - Facteurs de Risque Et Déterminants Moléculaires Des Maladies Liées Au Vieillissement, University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France",
        "Division of Intensive Care, Hôpital Roger Salengro, CHU de Lille, Lille, France"
      ],
      "name": "Sebastien Preau"
    },
    {
      "affiliations": [
        "General Intensive Care Unit, Sud Essonne Hospital, Etampes, France"
      ],
      "name": "Shidasp Siami"
    },
    {
      "affiliations": [
        "Médecine Intensive-Réanimation, District Hospital Center, La Roche-sur-Yon, France"
      ],
      "name": "Caroline Pouplet"
    },
    {
      "affiliations": [
        "Médecine Intensive-Réanimation, CH de Haguenau, Haguenau, France"
      ],
      "name": "Asaël Berger"
    },
    {
      "affiliations": [
        "Service de Réanimation Polyvalente et Surveillance Continue, Assistance Publique-Hôpitaux de Paris, Université Paris Saclay, Hôpital Antoine Béclère, Clamart, France"
      ],
      "name": "Charles Damoisel"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, HCL de Lyon, Hôpital Edouard Herriot, Lyon, France"
      ],
      "name": "Laurent Argaud"
    },
    {
      "affiliations": [
        "Service de Réanimation, CH de Dieppe, Dieppe, France"
      ],
      "name": "Jean Philippe Rigaud"
    },
    {
      "affiliations": [
        "Service de Réanimation Polyvalente, Centre Hospitalier de Valenciennes, Valenciennes, France"
      ],
      "name": "Fabien Lambiotte"
    },
    {
      "affiliations": [
        "Service Médecine Intensive et Réanimation, CHU de Montpellier, Montpellier, France"
      ],
      "name": "Kada Klouche"
    },
    {
      "affiliations": [
        "Service de Réanimation Polyvalente, Groupe hospitalier Paris Saint-Joseph, Paris, France"
      ],
      "name": "Cedric Bruel"
    },
    {
      "affiliations": [
        "Medical Intensive Care Unit, Strasbourg University Nouvel Hôpital Civil, Strasbourg, France"
      ],
      "name": "Raphael Clere-Jehl"
    },
    {
      "affiliations": [
        "Medical Intensive Care Unit Department, AP-HP, Saint-Louis University Hospital, Paris-Cité University, Paris, France",
        "INSERM UMR1342, Institut de Recherche Saint-Louis, Paris, France"
      ],
      "name": "Michael Darmon"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France"
      ],
      "name": "Julien Maizel"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive-Réanimation, Université Bourgogne-Europe, CHU Dijon-Bourgogne, Dijon, France",
        "Centre d’Investigation Clinique, module épidémiologie clinique, INSERM, CIC 1432, Université Bourgogne Europe, CHU Dijon Bourgogne, Dijon, France",
        "Equipe Lipness UMR 1231, 21, Université Bourgogne-Europe, CHU Dijon-Bourgogne, Dijon, France"
      ],
      "name": "Jean-Pierre Quenot"
    },
    {
      "affiliations": [
        "Agence générale des équipements et produits de santé, Assistance Publique Hôpitaux de Paris, Paris, France"
      ],
      "name": "Charreteur Robin"
    },
    {
      "affiliations": [
        "Institut Hospitalo Universitaire IHU-3 SEPSIS Institute, Garches, France"
      ],
      "name": "Jerome Fleuriet"
    },
    {
      "affiliations": [
        "Paris Saclay Ouest Clinical Research Unit, Ambroise Paré Hospital, AP-HP, Boulogne-Billancourt, France"
      ],
      "name": "Madalina Jacota"
    },
    {
      "affiliations": [
        "Université Versailles St Quentin and INSERM U1331 STAMPM, Institut Curie, Paris, France"
      ],
      "name": "Xavier Paoletti"
    },
    {
      "affiliations": [
        "Department of Intensive Care, APHP University Versailles Saint Quentin-University Paris Saclay, Hopital Raymond-Poincare, Garches, France",
        "Institut Hospitalo Universitaire IHU-3 SEPSIS Institute, Garches, France",
        "Laboratory of Infection & Inflammation-U1173, School of Medicine, INSERM, University Versailles Saint Quentin-University Paris Saclay, Garches, France"
      ],
      "name": "Djillali Annane"
    },
    {
      "affiliations": [
        "Department of Intensive Care, APHP University Versailles Saint Quentin-University Paris Saclay, Hopital Raymond-Poincare, Garches, France",
        "Institut Hospitalo Universitaire IHU-3 SEPSIS Institute, Garches, France",
        "Laboratory of Infection & Inflammation-U1173, School of Medicine, INSERM, University Versailles Saint Quentin-University Paris Saclay, Garches, France",
        "Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care, Pitié-Salpêtrière Hospital, Paris, France",
        "Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire (CHU) d’Orléans, Orleans, France",
        "LI²RSO, Université d’Orléans, Château de la Source, Orléans, France",
        "Service de Médecine Intensive Réanimation, Hôpital Nord Franche-Comté - Site de Belfort, Belfort, France",
        "U1167 - RID-AGE - Facteurs de Risque Et Déterminants Moléculaires Des Maladies Liées Au Vieillissement, University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France",
        "Division of Intensive Care, Hôpital Roger Salengro, CHU de Lille, Lille, France",
        "General Intensive Care Unit, Sud Essonne Hospital, Etampes, France",
        "Médecine Intensive-Réanimation, District Hospital Center, La Roche-sur-Yon, France",
        "Médecine Intensive-Réanimation, CH de Haguenau, Haguenau, France",
        "Service de Réanimation Polyvalente et Surveillance Continue, Assistance Publique-Hôpitaux de Paris, Université Paris Saclay, Hôpital Antoine Béclère, Clamart, France",
        "Service de Médecine Intensive Réanimation, HCL de Lyon, Hôpital Edouard Herriot, Lyon, France",
        "Service de Réanimation, CH de Dieppe, Dieppe, France",
        "Service de Réanimation Polyvalente, Centre Hospitalier de Valenciennes, Valenciennes, France",
        "Service Médecine Intensive et Réanimation, CHU de Montpellier, Montpellier, France",
        "Service de Réanimation Polyvalente, Groupe hospitalier Paris Saint-Joseph, Paris, France",
        "Medical Intensive Care Unit, Strasbourg University Nouvel Hôpital Civil, Strasbourg, France",
        "Medical Intensive Care Unit Department, AP-HP, Saint-Louis University Hospital, Paris-Cité University, Paris, France",
        "INSERM UMR1342, Institut de Recherche Saint-Louis, Paris, France",
        "Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France",
        "Service de Médecine Intensive-Réanimation, Université Bourgogne-Europe, CHU Dijon-Bourgogne, Dijon, France",
        "Centre d’Investigation Clinique, module épidémiologie clinique, INSERM, CIC 1432, Université Bourgogne Europe, CHU Dijon Bourgogne, Dijon, France",
        "Equipe Lipness UMR 1231, 21, Université Bourgogne-Europe, CHU Dijon-Bourgogne, Dijon, France",
        "Agence générale des équipements et produits de santé, Assistance Publique Hôpitaux de Paris, Paris, France",
        "Paris Saclay Ouest Clinical Research Unit, Ambroise Paré Hospital, AP-HP, Boulogne-Billancourt, France",
        "Université Versailles St Quentin and INSERM U1331 STAMPM, Institut Curie, Paris, France"
      ],
      "name": "HORNBILL consortium"
    },
    {
      "affiliations": [],
      "name": "CRICS-TRIGGERSEP network"
    }
  ],
  "title": "HydrOcortisone and fludRocortisoNe for critical ILLness-related corticosteroid insufficiency (HORNbILL): study protocol for a multicentre randomised placebo-controlled trial",
  "uid": "c7265d81-32bf-50a1-8b57-f63e8c692a25"
}