The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial has previously demonstrated that low doses of corticosteroids reduce the risk of death by one-fifth for patients admitted to hospital for COVID-19 who require oxygen and by up to one-third for those who require more intensive ventilatory support. Consequently, this treatment is now widely used for such patients around the world.
There has been interest in whether using a higher dose of corticosteroids would provide additional benefits. Between 25 May 2021 and 13 May 2022, 1,272 hospitalised patients with COVID-19 and low oxygen levels in their blood (hypoxia) but not requiring non-invasive ventilation or invasive mechanical ventilation were randomised to receive higher dose corticosteroids or usual care alone.
Patients who were allocated to higher dose corticosteroids received 20mg dexamethasone once a day for five days followed by 10mg dexamethasone once a day for up to five days or until discharge from hospital if sooner. Patients who were allocated to usual care alone typically received 6mg dexamethasone once a day for ten days or until discharge from hospital if sooner.
Results from the RECOVERY trial published in The Lancet today demonstrate that in adult patients admitted to hospital for COVID-19 with low blood oxygen levels or receiving simple oxygen therapy but who do not require more intensive breathing support, using higher doses of corticosteroids results in a 60% increased risk of death compared to similar patients receiving usual care alone (which include lower dose corticosteroids).
Key findings
- There was a significant 60% increase in the primary endpoint of 28-day mortality (19% in the higher dose group vs. 12% in usual care group; rate ratio 1·59; 95% confidence interval 1·20-2·10; p=0·0012).
- There was also an excess of pneumonia reported due to non-COVID infection in the higher dose corticosteroid group (10% vs. 6%) and of hyperglycaemia (high blood sugar) requiring an increase in dose of insulin (22% vs. 14%) than in the usual care group.
Sir Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health, and Joint Chief Investigator for the RECOVERY trial, 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. We now know that is not the case for patients requiring simple oxygen but it remains an unanswered possibility for those requiring more intensive forms of respiratory support.’
Sir Peter Horby, Moh Family Foundation Professor of Emerging Infectious Diseases at the Pandemic Sciences Institute, 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 48,000 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.’
The results published in The Lancet today only describe the effects of higher dose corticosteroids in patients who are in hospital with moderate severity COVID-19 and requiring simple oxygen therapy only. On the advice of the Data Monitoring Committee, the RECOVERY trial is continuing to investigate the effects of higher dose corticosteroids in patients hospitalised for more severe COVID-19 requiring either non-invasive ventilation or invasive mechanical ventilation.
The RECOVERY trial is supported by grants to the University of Oxford from the National Institute of Health and Care Research, UK Research and Innovation, and Wellcome.