TY - JOUR
T1 - Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY)
T2 - a randomised, controlled, open-label, platform trial
AU - Abani, Obbina
AU - Abbas, Ali
AU - Abbas, Fatima
AU - Abbas, Joshua
AU - Abbas, Kasim
AU - Abbas, Mustafa
AU - Abbasi, Sadia
AU - Abbass, Hakam
AU - Abbott, Alfie
AU - Abbott, Alison
AU - Abdallah, Nabeel
AU - Abdelaziz, Ammar
AU - Abdelaziz, Ashraf
AU - Abdelfattah, Mohamed
AU - Abdelqader, Bushra
AU - Abdul, Audrey
AU - Abdul, Basir
AU - Abdul, Siddiqui
AU - Abdul Rasheed, Althaf
AU - Abdulakeem, Ajibode
AU - Abdul-Kadir, Rezan
AU - Abdullah, Abdullah
AU - Abdulmumeen, Abdulfatahi
AU - Abdul-Raheem, Rasheed
AU - Abdulshukkoor, Niyaz
AU - Abdusamad, Kula
AU - Abed El Khaleq, Yazeed
AU - Abedalla, Mai
AU - Abeer Ul Amna, Abeer
AU - Abel, Lynn
AU - Abernethy, Katrina
AU - Abeywickrema, Movin
AU - Abhinaya, Chandra
AU - Abidin, Affyarsyah
AU - Aboaba, Adebanke
AU - Aboagye-Odei, Abigail
AU - Aboah, Christopher
AU - Aboelela, Heba
AU - Abo-Leyah, Hani
AU - Abouelela, Karim
AU - Abou-Haggar, Ahmed
AU - Abouibrahim, Mahmoud
AU - Abousamra, Ahmed
AU - Abouzaid, Mona
AU - Abraham, Miriam
AU - Abraham, Tizzy
AU - Abraheem, Abraheem
AU - Abrams, Judith
AU - Abrams, Rebecca
AU - Lambert, Pauline
AU - Horby, Peter W.
AU - RECOVERY Collaborative Group
N1 - 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.
Publisher Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2023/5/6
Y1 - 2023/5/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85153865218&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37060915
U2 - 10.1016/S0140-6736(23)00510-X
DO - 10.1016/S0140-6736(23)00510-X
M3 - Article
C2 - 37060915
AN - SCOPUS:85153865218
SN - 0140-6736
VL - 401
SP - 1499
EP - 1507
JO - The Lancet
JF - The Lancet
IS - 10387
ER -