2 research outputs found
Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVIDâ19 (BariâSolidAct): a randomised, doubleâblind, placeboâcontrolled phase 3 trial
Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials
have focused specifcally 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 modifed intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49â69) 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
diference and 95% CI â0.1% [â8·3 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% (â3.2% [â9.0 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 signifcant interacâ
tion 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 particiâ
pants were on average 11 years older, with more comorbidities.
Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conâ
clude on a potential survival beneft 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 fndâ
ings warrant further investigation in other trials and real-world studies