The RECOVERY trial has previously demonstrated that dexamethasone at a dose of 6mg once daily for 10 days or until discharge (if sooner) significantly reduces 28-day mortality for patients admitted to hospital for COVID-19 who require oxygen (with or without non-invasive ventilation) and for patients on invasive mechanical ventilation or extra-corporeal membranous oxygenation (ECMO). As a consequence, dexamethasone 6 mg once daily is now widely recommended for treatment of such patients.
Since February 2021 (outside the UK) and December 2021 within the UK, we have been assessing the effects of a higher dose corticosteroid regimen* vs usual care (ie dexamethasone 6 mg once daily for up to 10 days) for adult patients admitted to hospital for COVID-19 and with clinical evidence of hypoxia (ie receiving oxygen or with oxygen saturations <92% on room air), including those requiring non-invasive ventilation, invasive mechanical ventilation or ECMO.
The RECOVERY Data Monitoring Committee met on Wednesday 11 May and has advised:
‘For patients being considered for treatment with high dose dexamethasone, we recommend stopping recruitment of patients who require no oxygen or simple oxygen only at the time of randomisation due to safety concerns. Follow-up of these patients should continue. However, we encourage continuing recruitment and follow-up of all those patients who, at randomisation, require either non-invasive ventilation, invasive mechanical ventilation or ECMO.’
This recommendation was made because of emerging evidence from the trial of increased 28-day mortality for those patients who, at randomisation, were hypoxic but on no oxygen or who were on simple oxygen alone and were allocated to higher dose dexamethasone compared to similar patients allocated to usual care alone.
On Friday 13 May, recruitment to the higher dose corticosteroid arm was closed for patients on no oxygen or simple oxygen only. Study investigators have been advised that this regimen should no longer be administered to such patients as part of the trial. Follow-up of all patients previously recruited is ongoing and full results are anticipated within about six weeks. We have notified the relevant regulatory authorities and ethics committees.
All other aspects of the trial remain unchanged. In particular, for patients on non-invasive ventilation, invasive mechanical ventilation, or ECMO, recruitment to the higher dose corticosteroid comparison remains open and is encouraged.
Sir Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health, and Joint Chief Investigator, said ‘The RECOVERY trial has already demonstrated that for patients requiring oxygen or other forms of respiratory support, dexamethasone at a relatively low dose of 6 mg once daily improves the chances of survival. This simple and inexpensive treatment is now common practice around the world and is estimated to have saved many hundreds of thousands of lives. There has been a question of whether larger doses might produce even bigger benefits. Based on the preliminary information we have at present, that is not the case for patients requiring simple oxygen but remains an unanswered possibility for those requiring more intensive forms of respiratory support.’
Sir Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and Joint Chief Investigator for the RECOVERY trial, said ‘RECOVERY remains the largest trial of treatments in patients hospitalised with COVID-19, with over 47,000 participants to date. We remain enormously grateful for the huge contribution made by patients and medical staff to the RECOVERY trial. With their help, four effective treatments for patients hospitalised for COVID-19 have been identified, substantially improving the chances of survival for these patients. RECOVERY continues to evaluate a range of treatments for COVID-19, including critical questions about the optimal dose and timing of corticosteroids.’
* Dexamethasone 20 mg (base) once daily by mouth, nasogastric tube or intravenous infusion for five days followed by 10 mg once daily by mouth, nasogastric tube or intravenous infusion for five days. (Details of the corticosteroid regimen for pregnant women are provided in the protocol).