Higher dose corticosteroids associated with a 60% increased risk of death in hypoxic COVID-19 patients requiring only non-invasive oxygen therapy (The Lancet / RECOVERY trial)

*Note: this is a joint press release from the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and The Lancet.  Please credit both the congress and the journal in your stories*

A new study to be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2023, Copenhagen 15-18 April), and published in The Lancet, shows that, compared with standard care that included low dose corticosteroid use, treating hypoxic COVID-19 patients needing only oxygen therapy or no breathing support with higher dose corticosteroids is associated with a 60% increased risk of death.

This study conducted by the RECOVERY Collaborative Group and led by Prof Sir Peter Horby and Prof Sir Martin Landray (both of the University of Oxford, UK) had already identified that low-dose corticosteroids reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support. Since May 2021, the RECOVERY trial has evaluated the use of a higher dose of corticosteroids in this patient group. However, in May 2022, the independent Data Monitoring Committee advised that this treatment assessment be stopped for those patients receiving oxygen alone or no breathing support. The trial continues to study the effects of high-dose corticosteroids for those needing non-invasive or invasive mechanical ventilation.

Eligible and consenting adult patients with COVID-19 and clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% in normal 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 at the lower 6 mg once daily dose for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants.

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 – meaning a 60% increased risk of mortality for the higher dose corticosteroid group.

There was also an excess of pneumonia reported to be due to non-COVID infection in the higher-dose corticosteroid group: 64 cases (10%) vs 37 cases (6%); and an increase in hyperglycaemia (high blood sugar episode) requiring an increased insulin dose: 142 [22%] vs 87 [14%].

The authors conclude: “Among hospitalised patients with COVID-19 who require oxygen or ventilatory support, low-dose corticosteroids reduce the risk of death. However, among patients requiring simple oxygen only, higher doses of corticosteroids increase the risk of death compared with low-dose corticosteroids. It remains unclear whether using a higher dose of corticosteroids is beneficial among patients requiring non-invasive or invasive ventilation—the RECOVERY trial continues to study this.”

Professor Sir Peter Horby, Professor of Emerging Infections and Global Health at the University of Oxford and the Director of the Pandemic Sciences Institute, University of Oxford, UK. E) peter.horby@ndm.ox.ac.uk 

Professor Sir Martin Landray, Professor of Medicine and Epidemiology, Oxford Population Health, University of Oxford, UK. E) martin.landray@ndph.ox.ac.uk

For further information or interview requests with the chief investigators, please contact Louise Phillips, Communications Officer, Oxford Population Health T) +44 (0)1865 617 824 E) Louise.Phillips@ndph.ox.ac.uk

Alternative contact Tony Kirby in the ECCMID Media Centre. T) +44 7834 385827 E) tony@tonykirby.com

Full details of the study protocol and related materials are available at www.recoverytrial.net.

The RECOVERY trial is conducted by Oxford Population Health’s registered clinical trials units in partnership with the Nuffield Department of Medicine. The trial is supported by a grant to the University of Oxford from UK Research and Innovation/ the National Institute for Health Research (NIHR), and by core funding provided by the Bill and Melinda Gates Foundation, the Foreign, Commonwealth & Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Oxford Biomedical Research Centre, NIHR Clinical Trials Unit Support Funding, and Wellcome. Funding for RECOVERY outside the UK is provided by Wellcome through the COVID-19 Therapeutics Accelerator.

The RECOVERY trial currently involves many thousands of doctors, nurses, pharmacists, and research administrators at 178 hospitals across the whole of the UK. In the UK, the trial is supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales and Northern Ireland.