6/28/23, 12:02 AM ACTT-4 Pathway Feedback Search Clinical Topics Home Studies ACTT 4 ACTT 4 Disease COVID 19 infection 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 N = 1010 58.0% male 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) https://web.pathway.md/studies/rectPDfzDCxZzHBYy 1/2 6/28/23, 12:02 AM ACTT-4 Pathway Primary outcome Rate of mechanical ventilation-free survival by day 29 87.6 % 87.6 87 65.7 % 43.8 % 21.9 % No significant difference 0.0 % Baricitinib Dexamethasone 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. Open reference URL https://web.pathway.md/studies/rectPDfzDCxZzHBYy 2/2