1. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial
- Author
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Stephan Ehrmann, Jie Li, Miguel Ibarra-Estrada, Yonatan Perez, Ivan Pavlov, Bairbre McNicholas, Oriol Roca, Sara Mirza, David Vines, Roxana Garcia-Salcido, Guadalupe Aguirre-Avalos, Matthew W Trump, Mai-Anh Nay, Jean Dellamonica, Saad Nseir, Idrees Mogri, David Cosgrave, Dev Jayaraman, Joan R Masclans, John G Laffey, Elsa Tavernier, Ahmad A Elshafei, Brady J Scott, Tyler Weiss, Ramandeep Kaur, Lauren J Harnois, Amanda Miller, Flor Cerda, Andrew Klein, Jacob R Burd, Kathleen Posa-Kearney, Matthew Trump, Julie Jackson, Trevor Oetting, Mark Greenwood, Lindsay Hazel, Lisa Kingery, Lindsey Morris, Joon Yong Moon, Julianne Garnett, Shijing Jia, Kristine Nelson, Camilla Giacomini, John Laffey, Aoife Brennan, Conor Judge, Maeve Kernan, Claire Kelly, Ritika Ranjan, Siobhan Casey, Kevin O'Connell, Evelyn Newell, David Gallagher, Alistair Nichol, Ger Curley, Miguel Ibarra Estrada, Roxana García-Salcido, Alexandra Vargas-Obieta, Sara A Aguirre-Díaz, Luz Alcántar-Vallín, Montserrat Alvarado-Padilla, Quetzalcóatl Chávez-Peña, José A López-Pulgarín, Julio C Mijangos-Méndez, Miguel Marín-Rosales, Jorge E García-Alvarado, Oscar G Baltazar-González, Maura C González-Guerrero, Paola G Gutiérrez Ramírez, Sean Gilman, Patrice Plamondon, Rachel Roy, Jason Shahin, Raham Ragoshai, Aasmine Kaur, Josie Campisi, Joseph Dahine, Stefanie Perron, Slimane Achouri, Ronald Racette, Anne Kulenkamp, Andrés Pacheco, Marina García-de-Acilu, Irene Dot, Laetitia Bodet-Contentin, Denis Garot, Emmanuelle Mercier, Charlotte Salmon Gandonnière, Marlène Morisseau, Youenn Jouan, Walid Darwiche, Annick Legras, Antoine Guillon, Pierre-François Dequin, Anne-Charlotte Tellier, Jean Reignier, Jean-Baptiste Lascarrou, Amélie Seguin, Luc Desmedt, Emmanuel Canet, Christophe Guitton, Rémy Marnai, Jean-Christophe Callahan, Mickaël Landais, Nicolas Chudeau, Cédric Darreau, Patrice Tirot, Marjorie Saint Martin, Charlene Le Moal, Grégoire Muller, Sophie Jacquier, Gwenaël Prat, Pierre Bailly, Nicola Ferrière, Arnaud W Thille, Jean-Pierre Frat, Clément Saccheri, Matthieu Buscot, Gaëtan Plantefève, Damien Contou, Damien Roux, Jean-Damien Ricard, Laura Federici, Noémie Zucman, Santiago Freita Ramos, Marc Amouretti, Sébastien Besset, Coralie Gernez, Agathe Delbove, Guillaume Voiriot, Alexandre Elabbadi, Muriel Fartoukh, Sébastien Préau, Raphaël Favory, Alexandre Pierre, Arnaud Sement, Nicolas Terzi, Florian Sigaud, Clara Candille, Emanuele Turbil, Julien Maizel, Clément Brault, Yoan Zerbib, Aurélie Joret, Cédric Daubin, Laurent Lefebvre, Alais Giraud, Adrien Auvet, Christophe Vinsonneau, Mehdi Marzouk, Jean-Pierre Quenot, Pascal Andreu, Marie Labruyère, Jean-Baptiste Roudaut, François Aptel, Alexandre Boyer, Philippe Boyer, Jean-Claude Lacherade, Hugo Hille, Marie Bouteloup, Matthieu Jeannot, Marc Feller, Guillaume Grillet, Bruno Levy, Antoine Kimmoun, Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Adult ,Pulmonary and Respiratory Medicine ,Canada ,medicine.medical_specialty ,medicine.medical_treatment ,medicine.disease_cause ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Patient Positioning ,03 medical and health sciences ,0302 clinical medicine ,Correspondence ,Prone Position ,medicine ,Humans ,Intubation ,Prospective Studies ,030212 general & internal medicine ,Wakefulness ,Mexico ,ComputingMilieux_MISCELLANEOUS ,SARS-CoV-2 ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,COVID-19 ,United States ,3. Good health ,Prone position ,Treatment Outcome ,030228 respiratory system ,Respiratory failure ,Spain ,Relative risk ,Emergency medicine ,Observational study ,France ,Respiratory Insufficiency ,business ,Ireland ,Nasal cannula - Abstract
Summary Background Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. Methods In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov , NCT04325906 , NCT04347941 , NCT04358939 , NCT04395144 , NCT04391140 , and NCT04477655 . Findings Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75−0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62−0·91), and the HR for mortality was 0·87 (0·68−1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. Interpretation Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. Funding Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interregional, Appel d'Offre 2020, Groupement Interregional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion a Tours de la Reanimation Medicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.
- Published
- 2021