학술논문

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, JulienMeziani, FerhatDellamonica, JeanCordier, Pierre-YvesAllardet-Servent, JeromeFraisse, MeganVelly, LionelBarbar, Saber DavideLehingue, SamuelGuervilly, ChristopheDesgrouas, MaximeCamou, FabricePiperoglou, ChristelleVely, FredericDemaria, OlivierKarakunnel, JoysonFares, JoannaBatista, LucianaRotolo, FedericoViotti, JulienBoyer-Chammard, AgnesLacombe, KarineLe Dault, ErwanCarles, MichelSchleinitz, NicolasVivier, EricSchleinitz, NicolasCarvelli, JulienGainnier, MarcBourenne, JérémyBichon, AmandineLe Saux, AudreyBouzana, FouadTilmont, AntoineCauchois, EmiCoularet, CharlotteBruder, NicolasVelly, LionelEbbo, MikaelVeit, VéroniqueJean, EstelleSimeone, PierreBlasco, ValéryVely, FrédéricPiperoglou, ChristelleCoutard, BrunoPastorino, BorisVillaroel, Maria SabaGarrido-Pradalie, EmilieAmichi, KahénaLarosa, AurélieBlondelon, AurélieInal, ImaneAmichi, KahénaDhorne, JeanDurieux, FrédériqueBrunet, JulieCohen, AnitaDeluca, BénédicteMalkoun, RichardDellamonica, JeanBuscot, MatthieuSaccheri, ClémentCarles, MichelDemonchy, ElisaCua, EricChirio, DavidCourjon, JohanRisso, KarineRigault, Marie-ChristineGazoppi, LoïcSalas, VirginieBouskila, NadègeTouitou, IritBreaud, SophieBoughdiri, NihedMarrane, GuillaumeMeziani, FerhatMerdji, HamidHelms, JulieMonier, AlexandraDemiselle, JulienJandeaux, Louise-MarieStuder, AntoineAllam, HayatThiebaut, LéonieHutt-Clauss, AnneLe Dault, ErwanCordier, Pierre-YvesSavini, HélèneClerc, AxelleSpadoni, SophieJavelle, EmilieClerc, AxelleChouaki-Benmansour, NassimaLe Garlantezec, PatrickLe Tohic, SarahAllardet-Servent, JérômeBenarous, LucasMadjarian, CorinneAouadenne-Mesbah, AssiaRognon, AmélieFraisse, MeganPlantefeve, GaétanBenrezzak, NasroDubief, EmelineChauvel, OliviaJamet, CharlotteDavide Barbar, SaberAmbert, AudreyLloret, SophieElotmani, LoubnaDubois, GrégoryMeyrieux, SéverineBarthelemi, LaurieLehingue, SamuelPoulet, AntoineBezirganyan, KristinaAsselate, BelkacemProvitolo, VincentLacombe, KarineBollens, DianeLetaillandier, CyrielleTran, ChristianSebire, ManuelaLamarque, JulieDeguenel-Nguyen, AnneDesgrouas, MaximeJacquier, SophieMuller, GrégoireBretagnol, AnneMathonnet, ArmelleBenzekri, DalilaBarbier, FrançoisMai-Anh, NayRunge, IsabelleKamel, ToufikMuller, LucieTellec, SophieGuervilly, ChristophePapazian, LaurentForel, Jean-MarieSanz, CélinePinglis, CamilleValera, SabineColombini, NathalieCamou, FabriceMourissoux, GaelleGuisset, OlivierIssa, NahémaPedenon-Peyrichout, DelphineDelaune, JeanLanglade, ClairePedeboscq, StéphaneLescure, XavierIsernia, ValentinaBachelard, AntoineFleurot, OdileLe Gac, SylvieDa Conceicao, OliviaJulia, ZelieChalal, LyndaOualit, LyndaKramer, LauraLe Grand, JenniferPoissy, JulienNseir, SaadallaMariller, LaureDelcoutre, ClaireBrice, SylvieLelievre, Jean-DanielGallien, SébastienCotellon, ChristineVindrios, WilliamMelica, GiovannaNatella, Pierre-AndréBourhis, MarionThiemele, AlakiDe Nailly, Delphine LefebvreMalvy, DenisDesclaux, ArnaudDucours, MailysPerreau, PaulineBoyer, AlexandreClouzeau, BenjaminBui, Hoang-NamBourgoin, NicolasKabala, AnnaGhezzoul, BellabesServant, VincentDjabarouti, 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).