The ‘RECOVERY’ trial has released a preliminary analysis showing azithromycin, an antibiotic, had no meaningful clinical benefit for patients hospitalised with COVID-19.
The ‘Randomised Evaluation of COVid-19 thERapY’ (RECOVERY) trial was funded by UK Research and Innovation (UKRI). It is part of the UKRI/Department of Health and Social Care/National Institute for Health Research (NIHR) COVID-19 rapid research response.
To provide real-time information in the pandemic, the results are available as a preprint on medRxiv. Full results will be made available as a peer-reviewed publication once follow-up has been completed for all participants.
Testing a range of potential treatments
In March 2020, the RECOVERY trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including azithromycin.
Azithromycin is a widely used antibiotic that also reduces inflammation, a key feature of severe COVID-19, and also has some activity against the virus responsible for COVID-19.
To date there has been no convincing evidence of its effect on clinical outcomes in COVID-19.
Over 20,000 patients
Over 20,000 patients have been enrolled in the RECOVERY trial so far from 176 NHS hospitals in the UK.
The azithromycin arm of the trial was closed on 27 November. In the view of the Trial Steering Committee, sufficient patients had been enrolled to establish clearly whether or not the drug had a meaningful benefit among patients hospitalised with COVID-19.
The preliminary analysis showed no significant difference in the primary endpoint of 28-day mortality (19% azithromycin vs 19% usual care). There was also no evidence of beneficial effects on the risk of progression to mechanical ventilation or length of hospital stay. The results were consistent in different subgroups of patients.
A total of 2,582 patients were randomised to azithromycin and compared with 5,182 patients randomised to usual care alone. Patients entered the study an average of eight days after the onset of symptoms. Follow-up is complete for 73% of the participants and will be fully complete by the end of December.
Guiding clinical care around the world
Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, and Chief Investigator for the trial, said:
Azithromycin has been widely used to treat COVID patients because of its theoretical potential to reduce lung inflammation. Our results show very clearly that for patients hospitalised with COVID-19 azithromycin is not an effective treatment. While that is disappointing, it is nonetheless an important result that will guide clinical care around the world.
Looking ahead, RECOVERY continues to study several promising treatments, including convalescent plasma and Regeneron’s antibody cocktail targeted at the virus. Further results are likely over the next couple of months.
Real benefits for patients
Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Deputy Chief Investigator, said:
We have seen time and again during this epidemic the importance of large randomised clinical trials in determining which of the many promising treatments deliver real benefits for patients.
Once again, we thank the thousands of NHS doctors, nurses, pharmacists, and research staff who have contributed to the RECOVERY trial and the quest for knowledge about how best to reduce the terrible burden of this disease. Above all we must thank the 20,000 patients who have taken part in this extraordinary and truly world-leading effort.
The improved care of COVID patients today is thanks to the selfless contribution of RECOVERY participants in the past – and in turn, the care of patients tomorrow will be better as a consequence of those volunteering today. Thank you.
The study authors note they did not study patients in the community and are not able to make conclusions about the effectiveness of azithromycin outside the hospital setting.
Negative results are important
Professor Fiona Watt, Executive Chair of the Medical Research Council (MRC), which helped fund the trial, said:
Although it is disappointing that azithromycin isn’t an effective treatment for hospitalised COVID-19 patients, negative results are important so that clinicians can focus patient care on drugs that have been shown to work. This is particularly vital for antibiotics like azithromycin, because inappropriate use of antibiotics contributes to bacteria in the body becoming resistant.
The UK’s RECOVERY trial, as the world’s largest randomised trial of potential COVID-19 treatments, plays a key role in providing evidence of which drugs for COVID-19 can help to save lives.
Further information
About the RECOVERY trial
Over 20, 000 patients have taken part in the trial and the azithromycin arm reported today is now the fourth result to come out of the RECOVERY trial.
The trial previously showed that neither hydroxychloroquine nor lopinavir (a treatment for HIV) are effective in this population.
By contrast, it showed very clearly that dexamethasone reduces the risk of death by about one-third among patients receiving ventilation and by one-fifth in those requiring oxygen alone (but with no benefit among those not requiring respiratory support).
Treatments being studied
The trial continues to study the following treatments, each compared with usual standard of care alone:
- 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)
- Regeneron’s antibody cocktail (a combination of monoclonal antibodies directed against coronavirus)
- aspirin (commonly used to thin the blood)
- colchicine (a commonly used anti-inflammatory drug).
Funding
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 UKRI and the NIHR and by core funding provided by:
- NIHR Oxford Biomedical Research Centre
- Wellcome
- Bill and Melinda Gates Foundation
- Foreign, Commonwealth & Development Office
- Health Data Research UK
- MRC Population Health Research Unit
- NIHR Clinical Trials Unit Support Funding.
The RECOVERY trial involves many thousands of doctors, nurses, pharmacists, and research administrators at 176 hospitals across the whole of the UK, supported by staff at:
- NIHR Clinical Research Network
- NHS DigiTrials
- Public Health England
- Department of Health & Social Care
- Intensive Care National Audit & Research Centre
- Public Health Scotland
- Secure Anonymised Information Linkage at University of Swansea
- NHS in England, Scotland, Wales and Northern Ireland.
Content provided by the University of Oxford.
Top image: Healthcare workers adjusting equipment to a COVID patient (credit: Tempura/GettyImages)