What is already known about this topic and why is it important?
In early 2020, as this protocol was being developed, there were no approved treatments for COVID-19, a disease induced by the novel coronavirus SARS-CoV-2 that emerged in China in late 2019. The UK New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) advised that several possible treatments should be evaluated, including Lopinavir-Ritonavir, low-dose corticosteroids, and Hydroxychloroquine. These groups also advised that other treatments will soon emerge that require evaluation. A World Health Organization (WHO) expert group issued broadly similar advice.
How will you carry out your study?
The protocol describes a randomised trial among patients hospitalised for COVID-19. All eligible patients are randomly allocated between several treatment arms, each to be given in addition to the usual standard of care in the participating hospital: No additional treatment vs lopinavir-ritonavir vs low-dose corticosteroids vs hydroxychloroquine vs azithromycin. In a factorial design, eligible patients are allocated simultaneously to no additional treatment vs convalescent plasma. The study allows a subsequent randomisation for patients with progressive COVID-19 (evidence of hyper-inflammatory state): No additional treatment vs tocilizumab.
How will you decide which patients are included in your study?
All patients admitted to hospital with proven or suspected SARS-CoV-2 infection are eligible for the trial.
How many patients do you anticipate including?
We have randomised >10,000 participants to date.
For how long will you follow up these patients?
We would like to follow them through routine data linkage (such as with UKRR) for 10 years from randomisation.
What value will UKRR data add to the project?
Linkage to the UKRR would also allow assessment of any effects of the treatments on the development of acute kidney injury following randomisation. Information on the use of renal replacement therapy within the first 28 days is already available from the follow-up forms completed by the site staff but the laboratory acute kidney injury alert data from the UKRR would allow more comprehensive assessment of renal outcomes. In addition the UKRR linkage would allow assessment of the effects of the trial treatments on the long-term risk of Chronic Kidney Disease and End Stage Kidney Failure following the initial acute illness. We would also wish to characterise our participants (eg, dialysis or transplant patients) at baseline using UKRR data.
What new information will your study generate and how will this benefit patients?
The trial will assess the efficacy and safety of the trial treatments in COVD-19 which will directly inform the care of millions of patients worldwide.
