Oxford, United Kingdom (Press Release) – In March 2020, the RECOVERY (Ran­domised Eval­u­a­tion of COVid-19 thERapY) trial was estab­lished as a ran­domised clin­i­cal trial to test a range of poten­tial treat­ments for COVID-19, in­clud­ing low-dose dexa­meth­a­sone (a steroid treat­ment). Over 11,500 patients have been en­rolled from over 175 NHS hos­pi­tals in the UK.

On 8 June, recruitment to the dexa­meth­a­sone arm was halted since, in the view of the trial Steering Com­mit­tee, suf­fi­cient patients had been en­rolled to estab­lish whether or not the drug had a meaningful ben­e­fit.

A total of 2104 patients were ran­domised to re­ceive dexa­meth­a­sone 6 mg once per day (either by mouth or by in­tra­venous in­jec­tion) for ten days and were com­pared with 4321 patients ran­domised to usual care alone. Among the patients who re­ceived usual care alone, 28-day mortality was highest in those who re­quired venti­la­tion (41%), intermediate in those patients who re­quired oxygen only (25%), and lowest among those who did not re­quire any res­pira­tory intervention (13%).

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% con­fi­dence in­ter­val 0.48 to 0.88]; p=0.0003) and by one fifth in other patients re­ceiv­ing oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no ben­e­fit among those patients who did not re­quire res­pira­tory sup­port (1.22 [0.86 to 1.75; p=0.14).

Based on these re­­sults, 1 death would be prevented by treat­ment of around 8 ventilated patients or around 25 patients re­quir­ing oxygen alone.

Given the pub­lic health importance of these re­­sults, we are now work­ing to pub­lish the full details as soon as possible.

Peter Horby, Pro­fessor of Emerging Infectious Diseases in the Nuffield ­De­part­ment of Medicine, Uni­ver­sity of Oxford, and one of the Chief In­ves­ti­ga­tors for the trial, said: ‘Dexamethasone is the first drug to be shown to im­prove sur­vival in COVID-19. This is an extremely welcome re­­sult. The sur­vival ben­e­fit is clear and large in those patients who are sick enough to re­quire oxygen treat­ment, so dexa­meth­a­sone should now be­come standard of care in these patients. Dexa­meth­a­sone is inexpensive, on the shelf, and can be used im­medi­ately to save lives world­wide.’

Martin Landray, Pro­fessor of Medicine and Epidemiology at the Nuffield ­De­part­ment of Population Health, Uni­ver­sity of Oxford, one of the Chief In­ves­ti­ga­tors, said: ‘Since the appearance of COVID-19 six months ago, the search has been on for treat­ments that can im­prove sur­vival, par­tic­u­larly in the sickest patients. These pre­lim­i­nary re­­sults from the RECOVERY trial are very clear – dexa­meth­a­sone reduces the risk of death among patients with severe res­pira­tory com­pli­ca­tions. COVID-19 is a global dis­ease – it is fantastic that the first treat­ment dem­onstrated to reduce mortality is one that is instantly avail­able and af­ford­able world­wide.’

About the RECOVERY trial

The RECOVERY trial is a large, ran­domised con­trolled trial of possible treat­ments for patients ad­mitted to hos­pi­tal with COVID-19. Over 11,500 patients have been ran­domised to the fol­low­ing treat­ment arms, or no addi­tional treat­ment:

• Lopinavir-Ritonavir (commonly used to treat HIV)
• Low-dose Dexa­meth­a­sone (a type of steroid, which typ­i­cally used to reduce inflammation)
• Hydroxychloroquine (which has now been stopped due to lack of ef­fi­cacy)
• Azithromycin (a commonly used antibiotic)
• Tocilizumab (an anti-in­flam­ma­tory treat­ment given by in­jec­tion)
• Convalescent plasma (collected from donors who have recovered from COVID-19 and con­tains anti­bodies against the SARS-CoV-2 virus).

Overall dexa­meth­a­sone reduced the 28-day mortality rate by 17% (0.83 [0.74 to 0.92]; P=0.0007) with a highly sig­nif­i­cant trend showing greatest ben­e­fit among those patients re­quir­ing venti­la­tion (test for trend p<0.001). But it is im­por­tant to recognise that we found no evi­dence of ben­e­fit for patients who did not re­quire oxygen and we did not study patients outside the hos­pi­tal setting. Follow-up is com­plete for over 94% of par­tic­i­pants.

The RECOVERY trial is con­ducted by the registered clin­i­cal trials units with the Nuffield ­De­part­ment of Population Health 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 / National In­sti­tute for Health Re­search (NIHR) and by core funding provided by NIHR Oxford Biomedical Re­search Centre, Well­come, the Bill and Melinda Gates Foundation, the ­De­part­ment for Inter­na­tional De­vel­op­ment, Health Data Re­search UK, the Medical Re­search Council Population Health Re­search Unit, and NIHR Clinical Trials Unit Support Funding.

The RECOVERY trial in­volves many thousands of doctors, nurses, pharmacists, and re­search admin­is­tra­tors at over 175 hos­pi­tals across the whole of the UK, sup­ported by staff at the NIHR Clinical Re­search Network, NHS DigiTrials, Public Health England, Public Health Scotland, ­De­part­ment of Health & Social Care, and the NHS in England, Scotland, Wales and Northern Ireland.

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

A range of poten­tial treat­ments have been sug­gested for COVID-19 but it has been unclear whether any of them will turn out to be more ef­fec­tive in im­prov­ing sur­vival than the usual standard of hos­pi­tal care which all patients will re­ceive.

About Oxford Uni­ver­sity

Oxford Uni­ver­sity has been placed num­ber 1 in the Times Higher Education World Uni­ver­sity Rank­ings for the third year running, and at the heart of this success is our ground-breaking re­search and inno­va­tion. Oxford is world-famous for re­search excellence and home to some of the most tal­ented people from across the globe. Our work helps the lives of millions, solving real-world prob­lems through a huge network of part­ner­ships and col­lab­o­rations. The breadth and in­ter­dis­ci­plin­ary nature of our re­search sparks imaginative and inventive insights and solu­tions. Through its re­search com­mer­cialisation arm, Oxford Uni­ver­sity Innovation, Oxford is the highest uni­ver­sity pat­ent filer in the UK and is ranked first in the UK for uni­ver­sity spinouts, having created more than 170 new com­pa­nies since 1988. Over a third of these com­pa­nies have been created in the past three years.

Source: Uni­ver­sity of Oxford.