Accès ouvert déclaré
2023
article
Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial
Sylvie Chevret, Lila Bouadma, Claire Dupuis, Charles Burdet, Jean‐François Timsit, Naima Beldjoudi, Céline Alloux, Fadila Amerali, Béatrice Andriss, Kamyl Baghli, Hélène Brocvielle, Florence Capelle, Ines Chibane, Sarra Dalibey, Nadia Ettalhaoui, Sabrine Lamri, Yohan Maurer, Jean-Marc Mintsa, Alice Oubahim, Marie-Capucine Tellier, Imane Zemihi, Lila Bouadma, Moustafa Abdel-Nabey, Billal Azzouguen, Ghenima Belkessa, E De Montmollin, Veronique Deiler, Claire Dupuis, Aline Fallet, Guillaume Franchineau, Tiphaine Girard, Alexandra Grinea, Pierre Jaquet, Laura Kramer, Fariza Lamara, Lucie Lefèvre, Mehdi Marzouk, Juliette Patrier, Simona Presente, Faiza Sayagh, Fabrice Sinnah, Romain Sonneville, Paul-Henri Wicky, Sylia Zmihi, Yves Cohen, Nathalie Barget, Rawan Belmokhtar, Sabrina Brahmi, Naoual Djabra, Nathan Ebstein, Souha Fliss, Amina Gourbdji, William Juguet, Fadhila Messani, T Rambaud, Vanessa Rathouin, Mani Rebai, Marthe Rigal, Julien Schmidt, Marie Soulié, Yacine Tandjaoui-Lombiotte, Anaïs Winchenne, Marianne Ziol, Romain Arrestier, François Bagate, Morgan Benais, Inès Bendib, LE Lan, Brice Benelli, Enora Berti, A Bertier, Guillaume Carteaux, M.E.T Carvalho, Pedro Cavaleiro, Nicolas Deprost, Otto Hartman, Anne-Fleur Haudebourg, Delphine Lefebvre De Nailly, Julien Lopinto, Sabrina Mahiou, Paul Masi, Gaël Michaud, Luiza Nait-Chabane, Fariza Ouali, François Perier, Keyvan Razazi, Thiziri Sadaoui, Alaki Thiemele, Samuel Tuffet, Flavien Autron, Pauline Boddaert, Sylvie Brice, Morgan Caplan, Amélie Cerf, Nicolas Cousin, Marie Cuvelliez, Claire Delcourte, Arthur Durand, Raphaël Favory, Ahmed El Kalioubie, Myrtille Gaudel, Alexandre Gaudet, Julien Goutay, Marion Houard, Emmanuelle Jaillette, M. Jourdain, G. Ledoux, Laure Mariller, Guillaume Millot, Anne-Sophie Moreau, Christopher Nilès, Saad Nseir, Thierry Onimus, Sébastien Preau, Aurélie Roucou, Anahita Rouzé, Ouriel Saura, Arthur Simonnet, Romain Tortuyaux, Hamid Merdji, Hayat Allam, J Cattelan, Raphaël Clere-Jehl, Julie Helms, Kévin Hilt, Anne Hutt-Clauss, C Kummerlen, Ferhat Meziani, Alexandra Monnier, Hassène Rahmani, Antoine Studer, Leonie Thiebaut, Aurélie Han Hew Wai, Charles Cerf, David Cortier, Jérôme Devaquet, Dimitri Frémont, Richard Galliot, F Juster, Mathilde Le-Marchand, Lucie Le-Meur, Mathilde Neuville, Emmanuel Roux, Guillaume Tachon, Camille Vassord-Dang, Benjamin Zuber, C Bruel, Marie-José Aroulanda, Bryan Berthet-Delteil, Juliette Courtiade-Malher, Alix de Chevigny, Candice Fontaine, Julien Fournier, Sonia Garrigou, Meryam Jardin-Szucs, François Philippart, Sophie Renet, Emmanuelle Sacco, Marc Tran, C Guitton, Delphine Bolle, Jean-Christophe Callahan, Nicolas Chudeau, Cédric Darreau, Séverine Guillarme, M Landais, Laurent Latrouite, Charlène Le Moal, Eliott Lebasnier, Marie-Hélène Leroyer, Rémy Marnai, Juliette Meunier, Catherine Naveau, Marjorie Saint-Martin, Alain Robert, Patrice Tirot, C Schwebel, Joanna Bougnaud, Clara Candille, Roselyne Collomb-Muret, Charlotte Cordier, Louis-Marie Galerneau, Côme Gerard, Pierre Nicolas, Amel Refes, Guillaume Rigault, Florian Sigaud, Nicolas Terzi, E H Terzi, Emmanuelle Turbil, Yann Vallod, Mireille Adda, Claire Bachelier, Marine Bereiziat, Lise Bernard, Radhia Bouzgarrou, Laure Calvet, Pierre Couhault, Elisabeth Coupez, Frédéric Duee, Armelle Gilard, Kévin Grapin, Francis Kinda, Guillaume Laurichesse, Jean-Mathias Liteaudon, Bertrand Souweine, François Thouy, Hervé Declercq, Descamps Dp, Anne Dewatine, Sabine Janowski, Catherine Senis, Christophe Vinsonneau, Éric Kipnis, Anne Bignon, Tchadie Bommenel, C Huriez, Matthieu Duprey, Pierre Garçon, Afef Hammami, Andréa Issad, Marie-Odile Jaccod-Deneuville, Safaâ Kachmar, Ly Van-Vong, Jonathan Zarka, Bruno Megarbane, Nicolas Deye, Aude Jacob, Isabelle Malissin, A Abou Mrad, Sébastian Voicu, Guillaume Géri, Hélène Chambrin-Lauvray, Ouarda Douache, Mathieu Godement, Romain Jouffroy, Edouard Jullien, Matthieu Petit, Antoine Vieillard-Baron, A C Cariou, Alexandre Boyer, P Pavese, B Giraudeau
3Citations signalées, ce qui n’est pas une note de qualité
11Institutions déclarées
1Pays d’affiliation déclarés
Rattachement africain : fr.
Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: The respective benefits of high and low doses of dexamethasone (DXM) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and acute respiratory failure (ARF) are controversial, with two large triple-blind RCTs reaching very important difference in the effect-size. In the COVIDICUS trial, no evidence of additional benefit of high-dose dexamethasone (DXM20) was found. We aimed to explore whether some specific patient phenotypes could benefit from DXM20 compared to the standard of care 6 mg dose of DXM (DXMSoC). METHODS: We performed a post hoc exploratory Bayesian analysis of 473 patients who received either DXMSoc or DXM20 in the COVIDICUS trial. The outcome was the 60 day mortality rate of DXM20 over DXMSoC, with treatment effect measured on the hazard ratio (HR) estimated from Cox model. Bayesian analyses allowed to compute the posterior probability of a more than trivial benefit (HR < 0.95), and that of a potential harm (HR > 1.05). Bayesian measures of interaction then quantified the probability of interaction (Pr Interact) that the HR of death differed across the subsets by 20%. Primary analyses used noninformative priors, centred on HR = 1.00. Sensitivity analyses used sceptical and enthusiastic priors, based on null (HR = 1.00) or benefit (HR = 0.95) effects. RESULTS: Overall, the posterior probability of a more than trivial benefit and potential harm was 29.0 and 51.1%, respectively. There was some evidence of treatment by subset interaction (i) according to age (Pr Interact, 84%), with a 86.5% probability of benefit in patients aged below 70 compared to 22% in those aged above 70; (ii) according to the time since symptoms onset (Pr Interact, 99%), with a 99.9% probability of a more than trivial benefit when lower than 7 days compared to a < 0.1% probability when delayed by 7 days or more; and (iii) according to use of remdesivir (Pr Interact, 91%), with a 90.1% probability of benefit in patients receiving remdesivir compared to 19.1% in those who did not. CONCLUSIONS: In this exploratory post hoc Bayesian analysis, compared with standard-of-care DXM, high-dose DXM may benefit patients aged less than 70 years with severe ARF that occurred less than 7 days after symptoms onset. The use of remdesivir may also favour the benefit of DXM20. Further analysis is needed to confirm these findings. TRIAL REGISTRATION: NCT04344730, date of registration April 14, 2020 ( https://clinicaltrials.gov/ct2/show/NCT04344730?term=NCT04344730&draw=2&rank=1 ); EudraCT: 2020-001457-43 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-001457-43 ).
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial
- Date Crossref
- 01/01/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Les institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Les sujets associés
COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchLong-Term Effects of COVID-19