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Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial
Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

Background: low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods: this randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) 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 dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings: between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation: in patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Funding: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.

0140-6736
1499-1507
Horby, Peter W.
8f921e75-4605-4fb8-bb2c-be66fac6bb96
Landray, Martin J.
d01ada28-e875-4386-891d-e27fb2b6a056
Basnyat, Buddha
f33c8afb-9ba2-42cb-99c4-01413999a755
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Fletcher, Sophie
d05721e8-8943-4f13-a1f5-4ba183741c89
RECOVERY Collaborative Group
Horby, Peter W.
8f921e75-4605-4fb8-bb2c-be66fac6bb96
Landray, Martin J.
d01ada28-e875-4386-891d-e27fb2b6a056
Basnyat, Buddha
f33c8afb-9ba2-42cb-99c4-01413999a755
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Fletcher, Sophie
d05721e8-8943-4f13-a1f5-4ba183741c89

RECOVERY Collaborative Group (2023) Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. The Lancet, 401 (10387), 1499-1507. (doi:10.1016/S0140-6736(23)00510-X).

Record type: Article

Abstract

Background: low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods: this randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) 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 dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings: between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation: in patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Funding: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.

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e-pub ahead of print date: 13 April 2023
Published date: 4 May 2023
Additional Information: Funding Information: We thank the thousands of patients who participated in this trial and the many doctors, nurses, pharmacists, and other allied health professionals. We would also like to thank research administrators at participating hospital organisations supported in the UK by staff at the National Institute of Health and Care Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health and Social Care, the Intensive Care National Audit and Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage (SAIL) at University of Swansea, and the National Health Service in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation (UKRI) and NIHR (MC_PC_19056), the Wellcome Trust (222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill & Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab, casirivimab and imdevimab, sotrovimab, and empagliflozin were provided through support from Roche, Regeneron, GSK, and Boehringer Ingelheim, respectively. Colchicine for use in Indonesia was provided by Combiphar. The views expressed in this publication are those of the authors and not necessarily those of the UK National Health Services, the NIHR, or the UK Department of Health and Social Care.

Identifiers

Local EPrints ID: 477089
URI: http://eprints.soton.ac.uk/id/eprint/477089
ISSN: 0140-6736
PURE UUID: 193a0b0a-92fc-4acd-b9e9-80ebb3d6e51f
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 25 May 2023 16:49
Last modified: 15 Jun 2024 01:40

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Contributors

Author: Peter W. Horby
Author: Martin J. Landray
Author: Buddha Basnyat
Author: Saul Faust ORCID iD
Author: Sophie Fletcher
Corporate Author: RECOVERY Collaborative Group

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