Background Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir–ritonavir improves outcomes in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir–ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir– ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91–1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91–1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99–1·20; p=0·092). Interpretation In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19.
Above all, we thank the thousands of patients who participated in this
study. We also thank the many doctors, nurses, pharmacists, other allied
health professionals, and research administrators at 176 National Health
Service (NHS) hospital organisations across the UK, supported by staff
at the National Institute for Health Research (NIHR) Clinical Research
Network, NHS DigiTrials, Public Health England, UK Department of
Health and Social Care, Intensive Care National Audit & Research
Centre, Public Health Scotland, National Records Service of Scotland,
Secure Anonymised Information Linkage at University of Swansea,
and the NHS in England, Scotland, Wales, and Northern Ireland.
The RECOVERY trial is supported by a grant to the University of Oxford
(Oxford, UK) from UK Research and Innovation and NIHR
(MC_PC_19056) and by core funding provided by NIHR Oxford
Biomedical Research Centre, Wellcome, the Bill & Melinda Gates
Foundation, the UK Department for International Development, Health
Data Research UK, the Medical Research Council (MRC) Population
Health Research Unit, the NIHR Health Protection Unit in Emerging
and Zoonotic Infections, and NIHR Clinical Trials Unit Support
Funding. TJ is supported by a grant from the UK MRC (MC_UU_0002/14)
and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001).
WSL is supported by core funding provided by NIHR Nottingham
Biomedical Research Centre. Abbvie contributed some supplies of
lopinavir–ritonavir for use in this study. Tocilizumab was provided free
of charge for this study by Roche. The views expressed in this
publication are those of the authors and not necessarily those of the
NHS, the NIHR, or the UK Department of Health and Social Care.
The authors have no conflict of interest or financial relationships
relevant to the submitted work to disclose. No form of payment was
given to anyone to produce the manuscript. All authors have completed
and submitted the ICMJE Form for Disclosure of Potential Conflicts of
Interest. The Nuffield Department of Population Health at the
University of Oxford has a staff policy of not accepting honoraria or
consultancy fees directly or indirectly from industry.