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

Autor: 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, Sarah, Djabarouti
Přispěvatelé: Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nouvel Hôpital Civil de Strasbourg, CHU Nice, Hopital l'Archet 1, Centre Hospitalier Universitaire de Nice (CHU Nice), Réanimation Polyvalente, HIA Laveran - Department of Intensive Care - Marseille, Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Victor Dupouy, Aix Marseille Université (AMU), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Nîmes University Hospital, Department of Intensive Care, Hôpital Saint-Joseph [Marseille], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Saint-André, Université de Bordeaux (UB), Innate Pharma, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HIA Laveran a Marseille, European Project: 694502,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,TILC(2017), European Project: 875102,MInflaTILC
Rok vydání: 2022
Předmět:
Zdroj: Critical Care Medicine
Critical Care Medicine, 2022, 50, pp.1788-1798. ⟨10.1097/ccm.0000000000005683⟩
ISSN: 0090-3493
1530-0293
DOI: 10.1097/ccm.0000000000005683
Popis: International audience; 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).
Databáze: OpenAIRE
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