Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report

Horby, Peter; Lim, Wei Shen; Emberson, Jonathan; Mafham, Marion; Bell, Jennifer; Linsell, Louise; Staplin, Natalie; Brightling, Christopher; Ustianowski, Andrew; Elmahi, Einas; Prudon, Benjamin; Green, Christopher; Felton, Timothy; Chadwick, David; Rege, Kanchan; Fegan, Christopher; Chappell, Lucy C; Faust, Saul N; Jaki, Thomas; Jeffery, Katie; Montgomery, Alan; Rowan, Kathryn; Juszczak, Edmund; Baillie, J Kenneth; Haynes, Richard; Landray, Martin J; RECOVERY Collaborative Group

Abstract

Background Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.

Methods The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.

Results 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).

Conclusions In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.

• Deposit Date: Feb 8, 2023
• Publicly Available Date: Feb 9, 2023
• Public URL: https://nottingham-repository.worktribe.com/output/4737035
• Publisher URL: https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1
• Additional Information: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.