Peter W Horby
Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial
Horby, Peter W; Emberson, Jonathan R; Thwaites, Louise; Campbell, Mark; Peto, Leon; Pessoa-Amorim, Guilherme; Staplin, Natalie; Hamers, Raph L; Amuasi, John; Nel, Jeremy; Kestelyn, Evelyne; Thanh Phong, Nguyen; Shrestha, Anil; Nasronudin, Nasronudin; Sarkar, Rahuldeb; Ngoc Thach, Pham; Paudel, Damodar; Sumardi, Uun; Stewart, Richard; Nelwan, Erni; Rawal, Manisha; Kenneth Baillie, J; Buch, Maya H; Faust, Saul N; Jaki, Thomas; Jeffery, Katie; Juszczak, Edmund; Knight, Marian; Shen Lim, Wei; Mafham, Marion; Montgomery, Alan; Mumford, Andrew; Rowan, Kathryn; Basnyat, Buddha; Haynes, Richard; Landray, Martin J
Authors
Jonathan R Emberson
Louise Thwaites
Mark Campbell
Leon Peto
Guilherme Pessoa-Amorim
Natalie Staplin
Raph L Hamers
John Amuasi
Jeremy Nel
Evelyne Kestelyn
Nguyen Thanh Phong
Anil Shrestha
Nasronudin Nasronudin
Rahuldeb Sarkar
Pham Ngoc Thach
Damodar Paudel
Uun Sumardi
Richard Stewart
Erni Nelwan
Manisha Rawal
J Kenneth Baillie
Maya H Buch
Saul N Faust
Thomas Jaki
Katie Jeffery
Professor ED JUSZCZAK ED.JUSZCZAK@NOTTINGHAM.AC.UK
PROFESSOR OF CLINICAL TRIALS AND STATISTICS IN MEDICINE
Marian Knight
Wei Shen Lim
Marion Mafham
Professor ALAN MONTGOMERY ALAN.MONTGOMERY@NOTTINGHAM.AC.UK
DIRECTOR NOTTINGHAM CLINICAL TRIALS UNIT
Andrew Mumford
Kathryn Rowan
Buddha Basnyat
Richard Haynes
Martin J Landray
Abstract
Background
Low dose corticosteroids (e.g., 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with clinical hypoxia but not receiving ventilatory support (the combination of non-invasive mechanical ventilation, including high-flow nasal oxygen, continuous positive airway pressure and bilevel positive airway pressure ventilation, and invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain.
Methods
This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) assessed multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients receiving ventilatory support were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. Recruitment closed on 31 March 2024 when funding for the trial ended. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).
Findings
Between 25 May 2021 and 9 January 2024, 477 COVID-19 patients receiving ventilatory support were randomly allocated to receive usual care plus higher dose corticosteroids vs. usual care alone (of whom 99% received corticosteroids during the follow-up period). Of those randomised, 221 (46%) were in Asia, 245 (51%) in the UK and 11 (2%) in Africa. 143 (30%) had diabetes mellitus. Overall, 86 (35%) of 246 patients allocated to higher dose corticosteroids vs. 86 (37%) of 231 patients allocated to usual care died within 28 days (rate ratio [RR] 0.87; 95% CI 0.64–1.18; p = 0.37). There was no significant difference in the proportion of patients discharged from hospital alive within 28 days (128 [52%] in the higher dose corticosteroids group vs. 120 [52%] in the usual care group; RR 1.04, 0.81–1.33]; p = 0.78). Among those not on invasive mechanical ventilation at baseline, there was no clear reduction in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (76 [37%] of 206 vs. 93 [45%] of 205; RR 0.79 [95% CI 0.63–1.00]; p = 0.05).
Interpretation
In patients hospitalised for COVID-19 receiving ventilatory support, we found no evidence that higher dose corticosteroids reduced the risk of death compared to usual care, which included low dose corticosteroids.
Citation
Horby, P. W., Emberson, J. R., Thwaites, L., Campbell, M., Peto, L., Pessoa-Amorim, G., Staplin, N., Hamers, R. L., Amuasi, J., Nel, J., Kestelyn, E., Thanh Phong, N., Shrestha, A., Nasronudin, N., Sarkar, R., Ngoc Thach, P., Paudel, D., Sumardi, U., Stewart, R., Nelwan, E., …Landray, M. J. (2025). Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. eClinicalMedicine, 81, Article 103080. https://doi.org/10.1016/j.eclinm.2025.103080
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 13, 2025 |
Online Publication Date | Feb 12, 2025 |
Publication Date | Mar 1, 2025 |
Deposit Date | Feb 14, 2025 |
Publicly Available Date | Feb 14, 2025 |
Journal | eClinical Medicine |
Electronic ISSN | 2589-5370 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 81 |
Article Number | 103080 |
DOI | https://doi.org/10.1016/j.eclinm.2025.103080 |
Keywords | COVID-19, Corticosteroid, Dexamethasone, Mortality, Clinical trial |
Public URL | https://nottingham-repository.worktribe.com/output/45313638 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S2589537025000124#ack0010 |
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Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial
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Publisher Licence URL
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Copyright Statement
Copyright Crown Copyright ©2025 Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
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