Repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir and interferon - to treat COVID-19 appear to have little or no effect on patients hospitalised for the disease, in terms of overall mortality, initiation of ventilation and duration of hospital stay. The interim findings from the WHO Solidarity trial, published in the New England Journal of Medicine (NEJM), followed 11,266 adults at 405 hospitals in 30 countries.
The study by an international team of scientists, which was co-ordinated by the World Health Organisation, compared the effects on major outcomes in hospital of the local standard of care alone (the care all patients usually receive) versus the local standard of care in addition to one of four potential drugs to treat COVID-19. The Bristol Trials Centre at the University of Bristol rapidly developed and deployed the first SOLIDARITY randomization system during March 2020.
Patients were aged over-18, with 2,750 randomly allocated to Remdesivir, 954 to hydroxychloroquine, 1,411 lopinavir, 651 interferon plus lopinavir, 1,412 only interferon, and 4,088 no study drug.
None of the study’s four repurposed antiviral drugs substantially reduced mortality (in unventilated patients or any other subgroup) or delayed the need for ventilation.
The global Solidarity trial is still recruiting about 2,000 patients per month, thanks to the contributions of nearly 500 hospitals, 1,500 clinicians and research staff and their patients. It will now rapidly evaluate promising new treatment options, such as new antivirals, immunomodulators and specific anti-SARS-Cov-2 monoclonal antibodies. Its primary objective is to provide reliable estimates on any effects of potential drugs to treat COVID-19 on in-hospital mortality in moderate and in severe COVID.
Jonathan Sterne , Professor of Medical Statistics and Epidemiology, University of Bristol and Deputy Director of the NIHR Bristol Biomedical Research Centre (NIHR Bristol BRC), said: “It’s disappointing the four treatments evaluated in the Solidarity trial did not substantially reduce mortality. But it is encouraging that the trial will continue to evaluate promising new treatment options.’
Chris Rogers , Professor of Medical Statistics and Clinical Trials and Director of the Bristol Trials Centre, added: “We are proud to have contributed to the rapid rollout of a large, international randomized trial during a public health emergency, in order to answer key public health questions. The findings give evidence to policy makers and clinicians worldwide in their fight against COVID-19.’
Dr Ana Maria Henao-Restrepo, Head of the WHO Research and Development Unit, said: “The WHO Solidarity trial results are a significant public health achievement, and we would like to acknowledge the Bristol Trials Centre. Without their work on randomization and the data collection tool, set up in record time, we would not have been able to start randomizing patients to the trial so early in the pandemic.’
‘ Repurposed antiviral drugs for Covid-19 — interim WHO solidarity trial results ’ by WHO Solidarity Trial Consortium in New England Journal of Medicine (NEJM)