Baricitinib plus Standard of Care for Hospitalised Adults with COVID-19 on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation: Results of a Randomized, Placebo-Controlled Trial.
E. W. Ely, A. V. Ramanan, C. E. Kartman, S. de Bono, R. Liao, M. L. B. Piruzeli, J. D. Goldman, J. F. K. Saraiva, S. Chakladar, V. C. Marconi,
Abstract
Background The oral, selective Janus kinase (JAK)1/JAK2 inhibitor baricitinib demonstrated efficacy in hospitalised adults with COVID-19. This study evaluates the efficacy and safety of baricitinib in critically ill adults with COVID-19 requiring invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO).
Methods COV-BARRIER was a global, phase 3, randomised, double-blind, placebo-controlled trial in patients with confirmed SARS-CoV-2 infection (ClinicalTrials.gov NCT04421027). This addendum trial added a critically ill cohort not included in the main COV-BARRIER trial. Participants on baseline IMV/ECMO were randomly assigned 1:1 to baricitinib 4-mg (n=51) or placebo (n=50) for up to 14 days in combination with standard of care (SOC). Prespecified endpoints included all-cause mortality through days 28 and 60, and number of ventilator-free days, duration of hospitalisation, and time to recovery through day 28. Efficacy and safety analyses included the intent-to-treat and safety populations, respectively.
Findings SOC included baseline systemic corticosteroid use in 86% of participants. Treatment with baricitinib significantly reduced 28-day all-cause mortality compared to placebo (39·2% vs 58·0%; hazard ratio [HR]=0·54 [95%CI 0·31–0·96]; p=0·030). One additional death was prevented for every six baricitinib-treated participants. Significant reduction in 60-day mortality was also observed (45·1% vs 62·0%; HR=0·56 [95%CI 0·33–0·97]; p=0·027).
Baricitinib-treated participants showed numerically more ventilator-free days (8.1 vs 5.5 days, p=0.21) and spent over 2 days less in the hospital than placebo-treated participants (23·7 vs 26·1 days, p=0·050). The rates of infections, blood clots, and adverse cardiovascular events were similar between treatment arms.
Interpretation In critically ill patients with COVID-19 already receiving IMV/ECMO, treatment with baricitinib as compared to placebo (in combination with SOC, including corticosteroids) showed mortality HR of 0·56, corresponding to a 44% relative reduction at 60 days. This is consistent with the mortality reduction observed in less severely ill hospitalised primary COV-BARRIER study population.
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