Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial.

COVID-19 antiviral therapy cardiac adverse events randomized controlled trials remdesivir

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
29 Mar 2024
Historique:
received: 28 09 2023
revised: 07 12 2023
accepted: 13 12 2023
medline: 29 3 2024
pubmed: 29 3 2024
entrez: 29 3 2024
Statut: aheadofprint

Résumé

We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses.

Sections du résumé

BACKGROUND BACKGROUND
We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases.
METHODS METHODS
This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates.
RESULTS RESULTS
Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68).
CONCLUSIONS CONCLUSIONS
Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses.

Identifiants

pubmed: 38552208
pii: 7637630
doi: 10.1093/cid/ciae170
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

Sandrine Couffin-Cadièrgues (S)
Hélène Esperou (H)
Bernd Lamprecht (B)
Michael Joannidis (M)
Alexander Egle (A)
Richard Greil (R)
Antoine Altdorfer (A)
Vincent Fraipont (V)
Leila Belkhir (L)
Maya Hites (M)
Gil Verschelden (G)
Violaine Tolsma (V)
David Bougon (D)
Agathe Delbove (A)
Marie Gousseff (M)
Nadia Saidani (N)
Guilhem Wattecamps (G)
Félix Djossou (F)
Loïc Epelboin (L)
Jean-Philippe Lanoix (JP)
Pierre-Alexandre Roger (PA)
Claire Andrejak (C)
Yoann Zerbib (Y)
Kevin Bouiller (K)
Catherine Chirouze (C)
Jean-Christophe Navellou (JC)
Alexandre Boyer (A)
Charles Cazanave (C)
Alexandre Duvignaud (A)
Didier Gruson (D)
Denis Malvy (D)
Henry Lessire (H)
Martin Martinot (M)
Pascal Andreu (P)
Mathieu Blot (M)
Lionel Piroth (L)
Jean Pierre Quenot (JP)
Olivier Epaulard (O)
Nicolas Terzi (N)
Karine Faure (K)
Emmanuel Faure (E)
Julien Poissy (J)
Saad Nseir (S)
Florence Ader (F)
Laurent Argaud (L)
Tristan Ferry (T)
Thomas Perpoint (T)
Vincent Piriou (V)
Jean-Christophe Richard (JC)
Julien Textoris (J)
Florent Valour (F)
Florent Wallet (F)
André Cabié (A)
Jean-Marie Turmel (JM)
Cyrille Chabartier (C)
Rostane Gaci (R)
Céline Robert (C)
Alain Makinson (A)
Vincent Le Moing (V)
Kada Klouche (K)
Olivier Hinschberger (O)
Joy Mootien (J)
Sébastien Gibot (S)
François Goehringer (F)
Antoine Kimmoun (A)
Benjamin Lefevre (B)
David Boutoille (D)
Emmanuel Canet (E)
Benjamin Gaborit (B)
Paul Le Turnier (P)
François Raffi (F)
Jean Reignier (J)
Johan Courjon (J)
Jean Dellamonica (J)
Sylvie Leroy (S)
Charles-Hugo Marquette (CH)
Paul Loubet (P)
Claire Roger (C)
Albert Sotto (A)
Cédric Bruel (C)
Benoît Pilmis (B)
Guillaume Geri (G)
Elisabeth Rouveix-Nordon (E)
Olivier Bouchaud (O)
Samy Figueiredo (S)
Stéphane Jaureguiberry (S)
Xavier Monnet (X)
Lila Bouadma (L)
François-Xavier Lescure (FX)
Nathan Peiffer-Smadja (N)
Jean-François Timsit (JF)
Yazdan Yazdanpanah (Y)
Solen Kerneis (S)
Marie Lachâtre (M)
Odile Launay (O)
Jean-Paul Mira (JP)
Julien Mayaux (J)
Valérie Pourcher (V)
Jérôme Aboab (J)
Flora Crockett (F)
Naomi Sayre (N)
Clément Dubost (C)
Cécile Ficko (C)
David Lebeaux (D)
Sébastien Gallien (S)
Armand Mekontso-Dessap (A)
Jérôme Le Pavec (J)
Francois Stefan (F)
Hafid Ait-Oufella (H)
Karine Lacombe (K)
Jean-Michel Molina (JM)
Murielle Fartoukh (M)
Gilles Pialoux (G)
Firouzé Bani-Sadr (F)
Bruno Mourvillier (B)
François Benezit (F)
Fabrice Laine (F)
Bruno Laviolle (B)
Yves Le Tulzo (Y)
Matthieu Revest (M)
Elisabeth Botelho-Nevers (E)
Amandine Gagneux-Brunon (A)
Guillaume Thiery (G)
François Danion (F)
Yves Hansmann (Y)
Ferhat Meziani (F)
Walid Oulehri (W)
Charles Tacquard (C)
Fanny Bounes-Vardon (F)
Guillaume Martin-Blondel (G)
Marlène Murris-Espin (M)
Béatrice Riu-Poulenc (B)
Vanessa Jeanmichel (V)
Eric Senneville (E)
Louis Bernard (L)
Denis Garot (D)
Jean Reuter (J)
Thérèse Staub (T)
Marc Berna (M)
Sandra Braz (S)
Joao Miguel Ferreira Ribeiro (JMF)
José-Artur Paiva (JA)
Roberto Roncon-Albuquerque (R)
Benjamin Leveau (B)

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Auteurs

Vida Terzić (V)

Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.
Clinical Research Safety Department, INSERM, Paris, France.

Joe Miantezila Basilua (J)

Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.
Clinical Research Safety Department, INSERM, Paris, France.

Nicolas Billard (N)

Department of Epidemiology, Biostatistics and Clinical Research, Hospital Bichat, APHP, Paris, France.

Lucie de Gastines (L)

Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.
Clinical Research Safety Department, INSERM, Paris, France.

Drifa Belhadi (D)

Department of Epidemiology, Biostatistics and Clinical Research, Hospital Bichat, APHP, Paris, France.
Université Paris Cité, IAME, INSERM, Paris, France.

Claire Fougerou-Leurent (C)

Pharmacology Unit, University Hospital Rennes; CIC Inserm 1414, University Hospital Rennes.

Nathan Peiffer-Smadja (N)

Infectious Diseases Department, Hôpital Bichat - Claude-Bernard, APHP, Paris, France.
Université Paris Cité, IAME, INSERM, Paris, France.

Noémie Mercier (N)

Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.
Clinical Research Safety Department, INSERM, Paris, France.

Christelle Delmas (C)

Pôle de Recherche Clinique, INSERM, Paris, France.

Assia Ferrane (A)

Pôle de Recherche Clinique, INSERM, Paris, France.

Aline Dechanet (A)

Department of Epidemiology, Biostatistics and Clinical Research, Hospital Bichat, APHP, Paris, France.

Julien Poissy (J)

Université de Lille, Inserm U1285, CHU Lille, Pôle de réanimation, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.

Hélène Espérou (H)

Pôle de Recherche Clinique, INSERM, Paris, France.

Florence Ader (F)

Département des Maladies infectieuses et tropicales, Hospices Civils de Lyon, F-69004, Lyon, and Centre International de Recherche en Infectiologie (CIRI), Inserm 1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, F-69007, France.

Maya Hites (M)

Clinic of Infectious Diseases, Hôpital Universitaire de Bruxelles (HUB)-Erasme, Brussels, Belgium.

Claire Andrejak (C)

Pulmonolgy Unit, University Hospital Amiens-Picardie, UR 4294 AGIR, Université Picardie Jules Verne, Amiens, France.

Richard Greil (R)

IIIrd Medical Department, Paracelsus Medical University Salzburg; Salzburg Cancer Research Institute-Center for clinical Cancer and Immunology Trials (SCRI-CCCIT); Cancer Cluster Salzburg; Austrian Group for Medical Tumor Therapy (AGMT).

José-Artur Paiva (JA)

Serviço de Medicina Intensiva, Centro Hospitalar Universitário São João, Porto, Portugal.

Thérèse Staub (T)

Centre Hospitalier de Luxembourg, 4 Rue Ernest Barblé, L-1210 Luxembourg, Luxembourg.

Evelina Tacconelli (E)

Infectious diseases, Dept. Diagnostic and Public Health, University of Verona, Italy.

Charles Burdet (C)

Department of Epidemiology, Biostatistics and Clinical Research, Hospital Bichat, APHP, Paris, France.

Dominique Costagliola (D)

Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), Paris, France.

France Mentré (F)

Department of Epidemiology, Biostatistics and Clinical Research, Hospital Bichat, APHP, Paris, France.
Université Paris Cité, IAME, INSERM, Paris, France.

Yazdan Yazdanpanah (Y)

Pharmacology Unit, University Hospital Rennes; CIC Inserm 1414, University Hospital Rennes.
Infectious Diseases Department, Hôpital Bichat - Claude-Bernard, APHP, Paris, France.
ANRS|Emerging Infectious Diseases, Paris, France.

Alpha Diallo (A)

Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.
Clinical Research Safety Department, INSERM, Paris, France.

Classifications MeSH