The aim of the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial, initiated in March 2020, is to identify treatments that may be beneficial for patients admitted to hospital with suspected or confirmed COVID-19. To date, the trial has enrolled more than 11,500 patients from over 175 NHS hospitals in the UK.
Recruitment to the dexamethasone arm of the study was halted on June 8th after it was deemed that sufficient patients had been enrolled to ascertain whether or not the drug had meaningful benefit in patients with COVID-19.
Significant reduction in mortality
Patients randomised to the dexamethasone arm of the study (n=2,104) received dexamethasone 6mg once daily orally or intravenously for 10 days.
Compared with usual care alone (n=4,321), dexamethasone reduced the number of deaths by 35% in ventilated patients (rate ratio 0.65 [95% CI 0.48-0.88]; p=0.0003) and by 20% in other patients receiving oxygen only (0.80 [0.67-0.96]; p=0.0021). Overall, dexamethasone reduced the 28-day mortality rate by 17% (0.83 [0.74-0.92]; p=0.0007).
No benefit of dexamethasone was demonstrated in patients who did not require respiratory support (1.22 [0.86-1.75]; p=0.14).
Based on these findings it is estimated that dexamethasone treatment would prevent one death for every eight ventilated patients treated with the drug or for every 25 patients requiring oxygen alone.
Inclusion in standard care protocol
The Government has authorised the immediate inclusion of dexamethasone into the standard NHS protocol for the treatment of all hospitalised adult COVID-19 patients requiring oxygen, including those on ventilators. Use of the drug in paediatric COVID-19 patients is still being studied.
In a letter to health professionals the UK’s Chief Medical Officers and the Medical Director of NHS England state that they would normally advise waiting for the full results of the study before changing practice to ensure that final analysis and peer review do not lead to different conclusions. They add: “However, given this clear mortality advantage with good significance, and with a well-known medicine which is safe under these circumstances we consider it is reasonable for practice to change in advance of the final paper.”
Sufficient stocks available
Additional stocks of the drug were purchased for use in the event of a positive trial outcome and as a result there are already sufficient supplies to treat over 200,000 people.
Commenting on the results the UK’s Chief Scientific Adviser, Sir Patrick Vallance, said: “This is tremendous news today from the RECOVERY trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine.
Other drugs being evaluated as part of the RECOVERY trial include lopinavir/ritonavir, azithromycin, tocilizumab and convalescent plasma (collected from donors who have recovered from COVID-19). Evaluation of hydroxychloroquine has already ceased due to lack of efficacy.