Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE]).

Autor:	Carvelli J; AP-HM, Department of Intensive Care, Réanimation des Urgences, Medecine Intensive & Reanimation, Timone University Hospital, Marseille, France.; Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France.; Aix-Marseille University, Marseille, France.; Department of Intensive Care, Médecine Intensive & Réanimation, Nouvel Hôpital Civil, Strasbourg University Hospital, INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg University, Strasbourg, France.; Department of Intensive Care, Medecine Intensive & Reanimation, Hôpital l'Archet 1, Nice University Hospital, Cote d'Azur University, UR2CA, Nice, France.; Department of Intensive Care, Réanimation Polyvalente, HIA Laveran, Marseille, France.; Department of Intensive Care, Hôpital Européen, Marseille, France.; Department of Intensive Care, Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France.; AP-HM, Department of Anesthesiology & Critical Care Medicine, Réanimation Polyvalente, Timone University Hospital, Institut Neuroscience Timone CNRS UMR-7289, Marseille, France.; Department of Intensive Care, Nîmes University Hospital, University of Montpellier, Nîmes, France.; Department of Intensive Care, Hôpital Saint-Joseph, Marseille, France.; AP-HM, Department of Intensive Care, Médecine Intensive Réanimation, North Hospital, Centre d'Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279Marseille, Marseille, France.; Department of Intensive Care, Medecine Intensive & Reanimation, Centre Hospitalier Régional d'Orléans, Orléans, France.; Department of Intensive Care, Bordeaux University Hospital, Hôpital Saint-André, University of Bordeaux, Bordeaux, France.; AP-HM, Timone University Hospital, Immunology, Marseille, France.; Innate Pharma, Marseille, France.; AP-HP, Tropical Medicine & Infectious Diseases, Saint-Antoine Univeristy Hospital, Sorbonne University, Inserm UMR-S1136 IPLESP, Paris, France.; Tropical Medicine & Infectious Diseases, HIA Laveran, Marseille, France.; Tropical Medicine & Infectious Diseases, Hôpital l'Archet 1, Nice Univeristy Hospital, Université Côte d'Azur, Inserm-C3M, Nice, France.; AP-HM, Internal Medicine Department, Timone University Hospital, Marseille, France., Meziani F; Department of Intensive Care, Médecine Intensive & Réanimation, Nouvel Hôpital Civil, Strasbourg University Hospital, INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg University, Strasbourg, France., Dellamonica J; Department of Intensive Care, Medecine Intensive & Reanimation, Hôpital l'Archet 1, Nice University Hospital, Cote d'Azur University, UR2CA, Nice, France., Cordier PY; Department of Intensive Care, Réanimation Polyvalente, HIA Laveran, Marseille, France., Allardet-Servent J; Department of Intensive Care, Hôpital Européen, Marseille, France., Fraisse M; Department of Intensive Care, Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France., Velly L; Aix-Marseille University, Marseille, France.; AP-HM, Department of Anesthesiology & Critical Care Medicine, Réanimation Polyvalente, Timone University Hospital, Institut Neuroscience Timone CNRS UMR-7289, Marseille, France., Barbar SD; Department of Intensive Care, Nîmes University Hospital, University of Montpellier, Nîmes, France., Lehingue S; Department of Intensive Care, Hôpital Saint-Joseph, Marseille, France., Guervilly C; Aix-Marseille University, Marseille, France.; AP-HM, Department of Intensive Care, Médecine Intensive Réanimation, North Hospital, Centre d'Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279Marseille, Marseille, France., Desgrouas M; Department of Intensive Care, Medecine Intensive & Reanimation, Centre Hospitalier Régional d'Orléans, Orléans, France., Camou F; Department of Intensive Care, Bordeaux University Hospital, Hôpital Saint-André, University of Bordeaux, Bordeaux, France., Piperoglou C; Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France.; AP-HM, Timone University Hospital, Immunology, Marseille, France., Vely F; Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France.; Aix-Marseille University, Marseille, France.; AP-HM, Timone University Hospital, Immunology, Marseille, France., Demaria O; Innate Pharma, Marseille, France., Karakunnel J; Innate Pharma, Marseille, France., Fares J; Innate Pharma, Marseille, France., Batista L; Innate Pharma, Marseille, France., Rotolo F; Innate Pharma, Marseille, France., Viotti J; Innate Pharma, Marseille, France., Boyer-Chammard A; Innate Pharma, Marseille, France., Lacombe K; AP-HP, Tropical Medicine & Infectious Diseases, Saint-Antoine Univeristy Hospital, Sorbonne University, Inserm UMR-S1136 IPLESP, Paris, France., Le Dault E; Tropical Medicine & Infectious Diseases, HIA Laveran, Marseille, France., Carles M; Tropical Medicine & Infectious Diseases, Hôpital l'Archet 1, Nice Univeristy Hospital, Université Côte d'Azur, Inserm-C3M, Nice, France., Schleinitz N; Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France.; Aix-Marseille University, Marseille, France.; AP-HM, Internal Medicine Department, Timone University Hospital, Marseille, France., Vivier E; Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France.; Aix-Marseille University, Marseille, France.; AP-HM, Timone University Hospital, Immunology, Marseille, France.; Innate Pharma, Marseille, France.
Jazyk:	angličtina
Zdroj:	Critical care medicine [Crit Care Med] 2022 Dec 01; Vol. 50 (12), pp. 1788-1798. Date of Electronic Publication: 2022 Oct 10.
DOI:	10.1097/CCM.0000000000005683
Abstrakt:	Objectives: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. Design: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. Setting: Twelve clinical sites in France (ICU and general hospitals). Patients: Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp o2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. Interventions: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. Measurements and Main Results: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7; p = 0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. Conclusions: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367). Competing Interests: Dr. Carvelli received support for article research from Innate Pharma. Drs. Carvelli, Allardet-Servent, Barbar, Desgrouas, Camou, Piperoglou, Viotti, Boyer-Chammard, Lacombe, Le Dault, Schleinitz, and Vivier disclosed the off-label product use of avdoralimab. Dr. Guervilly received funding from Xenios FMC. Dr. Demaria’s institution received funding from BPI. Drs. Demaria, Karakunnel, Fares, Batista, Boyer-Chammard, and Vivier received funding from innate pharma. Drs. Demaria, Karakunnel, Fares, Batista, Rotolo, Viotti, Boyer-Chammard, and Vivier disclosed that they are employees of Innate Pharma. Dr. Karakunnel received funding from Primevax Precision Biologics. Dr. Rotolo received funding from Sanofi. Dr. Viotti disclosed work for hire. Dr. Lacombe received funding from MSD, Gilead, Janssen, and ViiV Healthcare. Dr. Vivier disclosed that he is a cofounder, shareholder, and employee of Innate Pharma and that his spouse is a shareholder of Innate Pharma. The remaining authors have disclosed that they do not have any potential conflicts of interest. (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu