Contributors: Hôpital Corentin Celton Issy-les-Moulineaux; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO); Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); UFR Médecine Santé - Université Paris Cité (UFR Médecine UPCité); Université Paris Cité (UPCité); Universidad Complutense de Madrid = Complutense University of Madrid Madrid (UCM); Département d'Informatique et Santé Publique CHU HEGP (HEGP - Informatique); Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO); Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité); Service d'informatique médicale et biostatistiques CHU Necker; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); National Institute on Drug Abuse NIH, Bethesda, USA (NIDA); National Institutes of Health Bethesda, MD, USA (NIH); AP-HP. Université Paris Saclay; Laboratoire Interdisciplinaire des Sciences du Numérique (LISN); Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS); Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord; Université Paris-Saclay; Institut National de Recherche en Informatique et en Automatique (Inria); CEA- Saclay (CEA); Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Hôpital Cochin AP-HP; AP-HP/Universities/INSERM COVID-19 Research Collaboration and AP-HP COVID CDR Initiative: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal
Abstract: International audience ; Introduction: Chlorpromazine has been suggested as being potentially useful in patients with coronavirus disease 2019 (COVID-19) on the grounds of its potential antiviral and anti-inflammatory effects.Objective: The aim of this study was to examine the association between chlorpromazine use and mortality among adult patients hospitalized for COVID-19.Methods: We conducted an observational, multicenter, retrospective study at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of first prescription of chlorpromazine during hospitalization for COVID-19. The primary endpoint was death. Among patients who had not been hospitalized in intensive care units (ICUs), we compared this endpoint between those who received chlorpromazine and those who did not, in time-to-event analyses adjusted for patient characteristics, clinical markers of disease severity, and other psychotropic medications. The primary analysis used a Cox regression model with inverse probability weighting. Multiple sensitivity analyses were performed.Results: Of the 14,340 adult inpatients hospitalized outside ICUs for COVID-19, 55 patients (0.4%) received chlorpromazine. Over a mean follow-up of 14.3 days (standard deviation [SD] 18.2), death occurred in 13 patients (23.6%) who received chlorpromazine and 1289 patients (9.0%) who did not. In the primary analysis, there was no significant association between chlorpromazine use and mortality (hazard ratio [HR] 2.01, 95% confidence interval [CI] 0.75-5.40; p = 0.163). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67, 95% CI 0.91-3.06; p = 0.100) and a multivariable Cox regression that indicated a significant positive association (HR 3.10, 95% CI 1.31-7.34; p = 0.010).Conclusion: Our results suggest that chlorpromazine prescribed at a mean daily dose of 70.8 mg (SD 65.3) was not associated with reduced mortality.
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