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Published in: Critical Care Medicine, 2022, 50, pp.1788 - 1798. ⟨10.1097/ccm.0000000000005683⟩

Authors: 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

Summary

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 Spo 2 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).

Link to HAL – amu-03952765

Link to DOI – 10.1097/ccm.0000000000005683