{
  "abstract": "Introduction Sickle cell disease (SCD) is due to the mutation of haemoglobin (Hb), from HbA to HbS and characterised by recurrent vaso-occlusive crises (VOC), which can progress to acute chest syndrome (ACS), a leading cause of death in adults with SCD. Hypoxia is a key modifiable factor in the polymerisation of HbS and the pathogenesis of VOC. High-flow nasal oxygen (HFNO) delivers humidified gas at high oxygen concentrations and flow rates: the former may reverse sickling (metabolic effect) to accelerate VOC resolution and prevent ACS, while the latter may reduce the risk of ACS by mitigating hypercapnia and generating positive airway pressure that limits hypoventilation and atelectasis (pulmonary effect). The study hypothesises that HFNO is a safe and effective strategy for treating VOC and preventing secondary ACS, and will assess this using a multi-arm multi-stage (MAMS) trial design.Methods and analysis This is a prospective, multicentre, randomised, open-label controlled trial following an MAMS design with three phases and four arms: one control (low-flow oxygen) and three HFNO intervention arms with varying fraction of inspired oxygen levels (low, intermediate, high). The pilot stage will assess safety and feasibility, using the rate of cardiac and neurological events as the primary endpoint. In the activity stage, arms demonstrating acceptable safety will be compared for efficacy based on the rate of VOC resolution without complications by day 5, allowing selection of the most promising arm. The final efficacy stage will compare the selected HFNO strategy to control, with prevention of secondary ACS by day 14 as the primary endpoint. The study aims to enrol up to 350 VOC episodes in total.Ethics and dissemination The study has been granted ethical approval (CPP SUD MEDITERRANEE IV). Following the provision of informed consent, patients will be included in the study. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03976180.",
  "authors": [
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri-Mondor, AP-HP, Créteil, France",
        "Groupe de Recherche Clinique CARMAS, Université Paris Est Créteil (UPEC), Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, Créteil, France",
        "INSERM U955, Université Paris Est Créteil, Créteil, France"
      ],
      "name": "Armand Mekontso Dessap"
    },
    {
      "affiliations": [
        "Unité des Maladies Génétiques du Globule Rouge, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France"
      ],
      "name": "Anoosha Habibi"
    },
    {
      "affiliations": [
        "Département d’Aval des Urgences, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France"
      ],
      "name": "Constance Guillaud"
    },
    {
      "affiliations": [
        "Service d’Acceuil des Urgences, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France"
      ],
      "name": "Christian Kassasseya"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Hôpital Bretonneau, Tours, France"
      ],
      "name": "Charlotte Larrat"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, CHU de Nantes, Nantes, France"
      ],
      "name": "Maïté Agbakou"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Hôpital Delafontaine, Saint-Denis, France"
      ],
      "name": "Tona Tchoubou"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, CHU Grenoble Alpes, Grenoble, Auvergne-Rhône-Alpes, France"
      ],
      "name": "Clara Candille"
    },
    {
      "affiliations": [
        "Service d’Hématologie Clinique, Hôpital Saint Vincent de Paul, Groupe Hospitalier de l’Institut Catholique de Lille, Lille, France"
      ],
      "name": "Benjamin Carpentier"
    },
    {
      "affiliations": [
        "Service de Réanimation médico-chirurgicale et unité de soins continus, Centre Hospitalier Le Mans, Le Mans, France"
      ],
      "name": "Mickael Landais"
    },
    {
      "affiliations": [
        "French National reference center for sickle cell disease, Department of Internal Medicine, European Georges Pompidou Hospital, AP-HP, Paris-Cité University, Paris, France"
      ],
      "name": "Jean-Benoît Arlet"
    },
    {
      "affiliations": [
        "Groupe de Recherche Clinique CARMAS, Université Paris Est Créteil (UPEC), Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, Créteil, France",
        "Service de Médecine Intensive Réanimation, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, Île-de-France, France"
      ],
      "name": "Muriel Fartoukh"
    },
    {
      "affiliations": [
        "Service des Maladies infectieuses et tropicales, CHU de Bordeaux, Bordeaux, France"
      ],
      "name": "Arnaud Desclaux"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, CHU de Nantes, Nantes, France"
      ],
      "name": "Agathe Masseau"
    },
    {
      "affiliations": [
        "Service de réanimation médico-chirurgicale, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny, Île-de-France, France"
      ],
      "name": "Johanna Oziel"
    },
    {
      "affiliations": [
        "Intensive Care Unit, Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole, Toulouse, France"
      ],
      "name": "Sihem Bouharaoua"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Hôpital Louis-Mourier, AP-HP, Colombes, Île-de-France, France"
      ],
      "name": "Comlan Affo"
    },
    {
      "affiliations": [
        "Service des Urgences adultes Nord, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Damien Viglino"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Hôpital Saint-Antoine, Paris, Île-de-France, France"
      ],
      "name": "Latifatou Boukari"
    },
    {
      "affiliations": [
        "Service de Médecine intensive Réanimation, CH Sud Francilien, Corbeil-Essonnes, France"
      ],
      "name": "Luis Ensenyat Martin"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, CH Saint-Denis, Saint-Denis, Île-de-France, France"
      ],
      "name": "Stéphanie Ngo"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France"
      ],
      "name": "Nadia Anguel"
    },
    {
      "affiliations": [
        "Service de Médecine Interne - Immunologie, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France"
      ],
      "name": "Christelle Chantalat"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Hôpital Jean-Verdier, AP-HP, Bondy, France"
      ],
      "name": "Anne Bourgarit-Durand"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Centre Hospitalier Intercommunal de Créteil, Créteil, Île-de-France, France"
      ],
      "name": "Isabelle Genty"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Caroline Makowski"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, Île-de-France, France"
      ],
      "name": "Stéphanie Guillet"
    },
    {
      "affiliations": [
        "Service d’Immunologie Clinique et Maladies Infectieuses, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France"
      ],
      "name": "Giovanna Melica"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, France"
      ],
      "name": "François Lionnet"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, Hôpital Avicenne, AP-HP, Bobigny, France"
      ],
      "name": "Sylvain Le Jeune"
    },
    {
      "affiliations": [
        "Département de biothérapie, Hôpital Necker-Enfants Malades, AP-HP, Paris, Île-de-France, France"
      ],
      "name": "Laure Joseph"
    },
    {
      "affiliations": [
        "Service des Maladies infectieuses et tropicales adultes, Hôpital Necker-Enfants Malades, AP-HP, Paris, France"
      ],
      "name": "Fanny Lanternier"
    },
    {
      "affiliations": [
        "Service de Médecine Interne, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole, Toulouse, France"
      ],
      "name": "Pierre Cougoul"
    },
    {
      "affiliations": [
        "Reference Centre for Rare Red Blood Cell Disorders, CHU de Montpellier, Montpellier, France"
      ],
      "name": "Ivan Bertchansky"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, CH Mayotte, Mayotte, France"
      ],
      "name": "Yvonnick Boue"
    },
    {
      "affiliations": [
        "INSERM U955, Université Paris Est Créteil, Créteil, France",
        "Unité des Maladies Génétiques du Globule Rouge, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France"
      ],
      "name": "Pablo Bartolucci"
    },
    {
      "affiliations": [
        "Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri-Mondor, AP-HP, Créteil, France",
        "Groupe de Recherche Clinique CARMAS, Université Paris Est Créteil (UPEC), Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, Créteil, France",
        "INSERM U955, Université Paris Est Créteil, Créteil, France"
      ],
      "name": "Ségolène Gendreau"
    },
    {
      "affiliations": [
        "Service de Santé Publique, Unité de Recherche Clinique, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France",
        "Equipe Clinical Epidemiology and Ageing (CEpiA), IMRB, INSERM U955, Université Paris Est Créteil, Créteil, France"
      ],
      "name": "Etienne Audureau"
    }
  ],
  "title": "High flow oxygen for vaso-occlusive crisis: a multicentre, prospective, randomised, multi-arm, multi-stage clinical trial (OSONE)",
  "uid": "65606641-64df-5ba8-9afe-5214aafe940c"
}