ACTT-4
Trial question
Is baricitinib superior to dexamethasone in patients hospitalized with COVID-19 infection?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
42.0% female
58.0% male
N = 1010
1010 patients (420 female, 590 male)
Inclusion criteria: adult patients hospitalized with COVID-19 infection requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation
Key exclusion criteria: receipt of invasive mechanical ventilation; low GFR; neutropenia; lymphopenia; pregnancy; allergy to study medication
Interventions
N=516 baricitinib (oral dose of 4 mg baricitinib tablet for up to 14 days plus remdesivir and dexamethasone placebo for up to 10 days)
N=494 dexamethasone (intravenous injection of 6 mg dexamethasone plus remdesivir for up to 10 days and baricitinib placebo for up to 14 days)
Primary outcome
Rate of mechanical ventilation-free survival by day 29
87
87.6
87.6 %
65.7 %
43.8 %
21.9 %
0.0 %
Baricitinib
Dexamethasone
No significant difference ↔
No significant difference in the rate of mechanical ventilation-free survival by day 29 (87% vs. 87.6%; ARD -0.6, 95% CI -4.8 to 3.6)
Secondary outcomes
Significant increase in median time to recovery (6 days vs. 5 days; MD 1.04, 95% CI 0.91 to 1.19)
Significant increase in median time to one-category clinical improvement (5 days vs. 4 days; MD 1.03, 95% CI 0.9 to 1.18)
Significant increase in median duration of initial hospitalization (7 days vs. 6 days; MD 1, 95% CI 0.2 to 1.8)
Safety outcomes
No significant differences in serious adverse events, new infections, VTE.
Significant differences in ≥1 adverse event (30% vs. 37%), ≥ 1 severe or life-threatening grade 3 or 4 adverse event (28% vs. 36%), ≥1 treatment-related adverse event (4% vs. 10%).
Conclusion
In adult patients hospitalized with COVID-19 infection requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib was not superior to dexamethasone with respect to the rate of mechanical ventilation-free survival by day 29.
Reference
Cameron R Wolfe, Kay M Tomashek, Thomas F Patterson et al. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial. Lancet Respir Med. 2022 May 23;S2213-2600(22)00088-1.
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