e-Article
Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE])*
Document Type
Academic Journal
Author
Carvelli, Julien; Meziani, Ferhat; Dellamonica, Jean; Cordier, Pierre-Yves; Allardet-Servent, Jerome; Fraisse, Megan; Velly, Lionel; Barbar, Saber Davide; Lehingue, Samuel; Guervilly, Christophe; Desgrouas, Maxime; Camou, Fabrice; Piperoglou, Christelle; Vely, Frederic; Demaria, Olivier; Karakunnel, Joyson; Fares, Joanna; Batista, Luciana; Rotolo, Federico; Viotti, Julien; Boyer-Chammard, Agnes; Lacombe, Karine; Le Dault, Erwan; Carles, Michel; Schleinitz, Nicolas; Vivier, Eric; Schleinitz, Nicolas; Carvelli, Julien; Gainnier, Marc; Bourenne, Jérémy; Bichon, Amandine; Le Saux, Audrey; Bouzana, Fouad; Tilmont, Antoine; Cauchois, Emi; Coularet, Charlotte; Bruder, Nicolas; Velly, Lionel; Ebbo, Mikael; Veit, Véronique; Jean, Estelle; Simeone, Pierre; Blasco, Valéry; Vely, Frédéric; Piperoglou, Christelle; Coutard, Bruno; Pastorino, Boris; Villaroel, Maria Saba; Garrido-Pradalie, Emilie; Amichi, Kahéna; Larosa, Aurélie; Blondelon, Aurélie; Inal, Imane; Amichi, Kahéna; Dhorne, Jean; Durieux, Frédérique; Brunet, Julie; Cohen, Anita; Deluca, Bénédicte; Malkoun, Richard; Dellamonica, Jean; Buscot, Matthieu; Saccheri, Clément; Carles, Michel; Demonchy, Elisa; Cua, Eric; Chirio, David; Courjon, Johan; Risso, Karine; Rigault, Marie-Christine; Gazoppi, Loïc; Salas, Virginie; Bouskila, Nadège; Touitou, Irit; Breaud, Sophie; Boughdiri, Nihed; Marrane, Guillaume; Meziani, Ferhat; Merdji, Hamid; Helms, Julie; Monier, Alexandra; Demiselle, Julien; Jandeaux, Louise-Marie; Studer, Antoine; Allam, Hayat; Thiebaut, Léonie; Hutt-Clauss, Anne; Le Dault, Erwan; Cordier, Pierre-Yves; Savini, Hélène; Clerc, Axelle; Spadoni, Sophie; Javelle, Emilie; Clerc, Axelle; Chouaki-Benmansour, Nassima; Le Garlantezec, Patrick; Le Tohic, Sarah; Allardet-Servent, Jérôme; Benarous, Lucas; Madjarian, Corinne; Aouadenne-Mesbah, Assia; Rognon, Amélie; Fraisse, Megan; Plantefeve, Gaétan; Benrezzak, Nasro; Dubief, Emeline; Chauvel, Olivia; Jamet, Charlotte; Davide Barbar, Saber; Ambert, Audrey; Lloret, Sophie; Elotmani, Loubna; Dubois, Grégory; Meyrieux, Séverine; Barthelemi, Laurie; Lehingue, Samuel; Poulet, Antoine; Bezirganyan, Kristina; Asselate, Belkacem; Provitolo, Vincent; Lacombe, Karine; Bollens, Diane; Letaillandier, Cyrielle; Tran, Christian; Sebire, Manuela; Lamarque, Julie; Deguenel-Nguyen, Anne; Desgrouas, Maxime; Jacquier, Sophie; Muller, Grégoire; Bretagnol, Anne; Mathonnet, Armelle; Benzekri, Dalila; Barbier, François; Mai-Anh, Nay; Runge, Isabelle; Kamel, Toufik; Muller, Lucie; Tellec, Sophie; Guervilly, Christophe; Papazian, Laurent; Forel, Jean-Marie; Sanz, Céline; Pinglis, Camille; Valera, Sabine; Colombini, Nathalie; Camou, Fabrice; Mourissoux, Gaelle; Guisset, Olivier; Issa, Nahéma; Pedenon-Peyrichout, Delphine; Delaune, Jean; Langlade, Claire; Pedeboscq, Stéphane; Lescure, Xavier; Isernia, Valentina; Bachelard, Antoine; Fleurot, Odile; Le Gac, Sylvie; Da Conceicao, Olivia; Julia, Zelie; Chalal, Lynda; Oualit, Lynda; Kramer, Laura; Le Grand, Jennifer; Poissy, Julien; Nseir, Saadalla; Mariller, Laure; Delcoutre, Claire; Brice, Sylvie; Lelievre, Jean-Daniel; Gallien, Sébastien; Cotellon, Christine; Vindrios, William; Melica, Giovanna; Natella, Pierre-André; Bourhis, Marion; Thiemele, Alaki; De Nailly, Delphine Lefebvre; Malvy, Denis; Desclaux, Arnaud; Ducours, Mailys; Perreau, Pauline; Boyer, Alexandre; Clouzeau, Benjamin; Bui, Hoang-Nam; Bourgoin, Nicolas; Kabala, Anna; Ghezzoul, Bellabes; Servant, Vincent; Djabarouti, Sarah
Source
Critical Care Medicine. Dec 01, 2022 50(12):1788-1798
Subject
Language
English
ISSN
0090-3493
Abstract
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 SpO2 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).