• Critical care medicine · Dec 2022

    Randomized Controlled Trial

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

    • Julien Carvelli, Ferhat Meziani, Jean Dellamonica, Pierre-Yves Cordier, Jerome Allardet-Servent, Megan Fraisse, Lionel Velly, Saber Davide Barbar, Samuel Lehingue, Christophe Guervilly, Maxime Desgrouas, Fabrice Camou, Christelle Piperoglou, Frederic Vely, Olivier Demaria, Joyson Karakunnel, Joanna Fares, Luciana Batista, Federico Rotolo, Julien Viotti, Agnes Boyer-Chammard, Karine Lacombe, Erwan Le Dault, Michel Carles, Nicolas Schleinitz, Eric Vivier, and FOR COVID Elimination (FORCE) Study Group.
    • AP-HM, Department of Intensive Care, Réanimation des Urgences, Medecine Intensive & Reanimation, Timone University Hospital, Marseille, France.
    • Crit. Care Med. 2022 Dec 1; 50 (12): 178817981788-1798.

    ObjectivesSevere COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19.DesignFOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study.SettingTwelve clinical sites in France (ICU and general hospitals).PatientsPatients 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.InterventionsPatients 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 ResultsWe 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.ConclusionsIn 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).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.

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