Lopinavir-ritonavir is not an effective treatment for patients admitted to the hospital with coronavirus disease 2019 (COVID-19), according to the results of a large randomized trial published in The Lancet.1
Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies.1 Results from a previous randomized trial of lopinavir-ritonavir conducted in199 patients admitted to hospital with COVID-19 showed no improvement in viral load, duration of hospital stay, or mortality.2 However, the trial was too small to rule out the possibility of clinically relevant benefits.2 Therefore, researchers in the United Kingdom conducted a randomized controlled, open-label, platform trial (RECOVERY; ClinicalTrials.gov Identifier: NCT04381936) to report the effects of lopinavir-ritonavir in patients admitted to the hospital with COVID-19.1
Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive usual care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) and 3424 patients to receive usual care. The researchers found no significant difference between the lopinavir-ritonavir group and the usual care group in terms of 28-day mortality (rate ratio, 0.98; 95% CI, 0.91-1.05; P =.53), the probability of discharge alive within 28 days, or, in patients who were not receiving invasive mechanical ventilation at time of randomization, the probability of progressing to the composite outcome of invasive mechanical ventilation or death (risk ratio, 1.09; 95% CI, 0.99-1.20; P =.092). Furthermore, there was no evidence of benefit of lopinavir-ritonavir in any of the patient subgroups.
“Our finding of no clinical benefit from lopinavir-ritonavir treatment compared with standard care supports earlier findings from a smaller clinical trial,” the study authors wrote. “Many clinical care guidelines have recommended lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19. These guidelines should be updated.”1
1. RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. Published online October 5, 2020. doi:10.1016/S0140-6736(20)32013-4
2. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-1799.