Title :

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

Author(s) :

Trøseid, Marius [Auteur]
Arribas, José R. [Auteur]
Assoumou, Lambert [Auteur]
Holten, Aleksander Rygh [Auteur]
Poissy, Julien [Auteur]
Hôpital Roger Salengro [Lille]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Terzić, Vida [Auteur]
Mazzaferri, Fulvia [Auteur]
Baño, Jesús Rodríguez [Auteur]
Eustace, Joe [Auteur]
Hites, Maya [Auteur]
Joannidis, Michael [Auteur]
Paiva, José-Artur [Auteur]
Reuter, Jean [Auteur]
Püntmann, Isabel [Auteur]
Patrick-Brown, Thale D. J. H. [Auteur]
Westerheim, Elin [Auteur]
Nezvalova-Henriksen, Katerina [Auteur]
Beniguel, Lydie [Auteur]
Dahl, Tuva Børresdatter [Auteur]
Bouscambert, Maude [Auteur]
Halanova, Monika [Auteur]
Péterfi, Zoltán [Auteur]
Tsiodras, Sotirios [Auteur]
Rezek, Michael [Auteur]
Briel, Matthias [Auteur]
Ünal, Serhat [Auteur]
Schlegel, Martin [Auteur]
Ader, Florence [Auteur]
Lacombe, Karine [Auteur]
Amdal, Cecilie Delphin [Auteur]
Rodrigues, Serge [Auteur]
Tonby, Kristian [Auteur]
Gaudet, Alexandre [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Heggelund, Lars [Auteur]
Mootien, Joy [Auteur]
Johannessen, Asgeir [Auteur]
Møller, Jannicke Horjen [Auteur]
Pollan, Beatriz Diaz [Auteur]
Tveita, Anders Aune [Auteur]
Kildal, Anders Benjamin [Auteur]
Richard, Jean-Christophe [Auteur]
Dalgard, Olav [Auteur]
Simensen, Victoria Charlotte [Auteur]
Baldé, Aliou [Auteur]
De Gastines, Lucie [Auteur]
Del Álamo, Marta [Auteur]
Aydin, Burç [Auteur]
Lund-Johansen, Fridtjof [Auteur]
Trabaud, Mary-Anne [Auteur]
Diallo, Alpha [Auteur]
Halvorsen, Bente [Auteur]
Røttingen, John-Arne [Auteur]
Tacconelli, Evelina [Auteur]
Yazdanpanah, Yazdan [Auteur]
Olsen, Inge C. [Auteur]
Costagliola, Dominique [Auteur]

Journal title :

Critical Care

Abbreviated title :

Crit Care

Volume number :

27

Pages :

9

Publisher :

BioMed Central

Publication date :

2023-01-10

ISSN :

1466-609X

English keyword(s) :

COVID-19
Vaccination
Safety
Baricitinib

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Santé publique et épidémiologie

English abstract : [en]

Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct ...
Show more >Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Research team(s) :

Immunité Pulmonaire

Submission date :

2024-01-19T22:26:46Z
2024-09-24T10:48:06Z