Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles EClinicalMedicine Year : 2022

Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group

Olivier Hermine (1, 2) , Xavier Mariette (3, 4) , Raphael Porcher (5, 6) , Felix Djossou (7, 8) , Yann Nguyen (9, 10) , Jean-Benoît Arlet (10, 11) , Laurent Savale (12, 3) , Jean Luc Diehl (11, 10) , Sophie Georgin-Lavialle (13, 14) , Jacques Cadranel (13, 14) , Gilles Pialoux (13, 14) , Karine Lacombe (15, 16, 17) , Arsène Mekinian (16, 15) , Hélène Gros (18) , Xavier Lescure (19) , Jade Ghosn (20) , Elisabeth Coupez (21) , Kevin Grapin (21) , Christophe Rapp (22) , Marc Michel (23, 24) , Anne Lise Lecapitaine (25) , Jean Marie Michot (26, 4, 27) , Nathalie Costedoat-Chalumeau (28, 29) , Liem Binh Luong Nguyen (28, 30) , Luca Semerano (31, 15) , François Raffi (32, 33) , Claire Aguillar (2, 34) , Claire Rouzaud (2, 35) , Jacques Eric Gottenberg (36, 37) , Yves Hansmann (36, 37) , Boris Bienvenu (38) , Jonathan London (39) , Franklin Samou Fantchou (40) , Felix Ackermann (41) , Antoine Gros (42) , Alexandre Morel (43) , Nicolas Gambier (44) , Damien Sène (45, 46) , Bruno Mégarbane (45, 47, 46) , Elie Azoulay (48, 46) , Serge Bureau (48, 49) , Maxime Dougados (28, 49) , Joseph Emmerich (35, 34) , Muriel Fartoukh (13, 14) , Bertrand Guidet (16, 14, 17) , Marc Humbert (11, 4) , Mathieu Mahevas (50, 24) , Frédéric Pène (28, 34) , Frédéric Schlemmer (50, 24) , Valérie Pourcher-Martinez (51, 14) , Annick Tibi (52) , Gabriel Baron (6, 5) , Elodie Perrodeau (5, 6) , Stéphanie Baron (11) , Gabriel Steg (19, 46) , Yazdan Yazdapanah (19, 10) , Tabassome Simon (16) , Matthieu Resche-Rigon (5, 48) , Pierre-Louis Tharaux (53) , Philippe Ravaud (5, 6)
1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 Hôpital Necker - Enfants Malades [AP-HP]
3 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
4 Université Paris-Saclay
5 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
6 Hôpital Hôtel-Dieu [Paris]
7 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
8 UMIT - Unité des Maladies Infectieuses et Tropicales
9 Hôpital Beaujon [AP-HP]
10 UPCité - Université Paris Cité
11 HEGP - Hôpital Européen Georges Pompidou [APHP]
12 HPPIT - Hypertension pulmonaire : physiopathologie et innovation thérapeutique
13 CHU Tenon [AP-HP]
14 USPC - Université Sorbonne Paris Cité
15 Université Sorbonne Paris Nord
16 CHU Saint-Antoine [AP-HP]
17 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
18 Hôpital Robert Ballanger [Aulnay-sous-Bois]
19 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
20 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
21 CHU Gabriel Montpied [Clermont-Ferrand]
22 Hôpital Américain de Paris
23 Hôpital Henri Mondor
24 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
25 CHCN - Centre Hospitalier Compiègne-Noyon
26 IGR - Institut Gustave Roussy
27 Département d'hématologie [Gustave Roussy]
28 Hôpital Cochin [AP-HP]
29 SU - Sorbonne Université
30 CIC 1417 - CIC Cochin Pasteur
31 Hôpital Avicenne [AP-HP]
32 Hôtel-Dieu de Nantes
33 CIC Nantes - Centre d’Investigation Clinique de Nantes
34 UPD5 - Université Paris Descartes - Paris 5
35 Centre hospitalier Saint-Joseph [Paris]
36 HUS - Les Hôpitaux Universitaires de Strasbourg
37 UNISTRA - Université de Strasbourg
38 Hôpital Saint-Joseph [Marseille]
39 Groupe Hospitalier Diaconesses Croix Saint-Simon
40 Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française]
41 Hôpital Foch [Suresnes]
42 CHV - Centre Hospitalier de Versailles André Mignot
43 HPA-RS - Hôpital privé d'Antony - Ramsay Santé
44 Hôpital Delafontaine
45 Hôpital Lariboisière-Fernand-Widal [APHP]
46 UPD7 - Université Paris Diderot - Paris 7
47 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
48 AP-HP - Hopital Saint-Louis [AP-HP]
49 UPE - Université Paris-Est
50 Hôpital Henri Mondor
51 CHU Pitié-Salpêtrière [AP-HP]
52 AGEPS - Agence Générale des Equipements et Produits de Santé [Paris]
53 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire

Abstract

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.
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Dates and versions

inserm-03787576 , version 1 (25-09-2022)

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Olivier Hermine, Xavier Mariette, Raphael Porcher, Felix Djossou, Yann Nguyen, et al.. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group. EClinicalMedicine, 2022, 46, pp.101362. ⟨10.1016/j.eclinm.2022.101362⟩. ⟨inserm-03787576⟩
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