Dr. Gibson
Clinical question: Does remdesivir have a mortality benefit in patients with COVID-19?
Background: The Solidarity trial previously reported preliminary mortality analyses for remdesivir, lopinavir, hydroxychloroquine, and interferon beta-1a use in COVID-19 inpatients. The latter three drugs were discontinued due to futility, but randomization to remdesivir continued. This review presents the final results of the Solidarity trial and all other relevant trials of remdesivir at the time of publication.
Study design: Randomized control trial and meta-analysis
Setting: Inpatients with COVID-19 infection from 454 hospitals in 35 countries in World Health Organization (WHO) regions between March 2020 and January 2021. These results were compared to a systematic review of the WHO Cochrane database for published COVID-19 treatment randomized inpatient trials.
Synopsis: A total of 8,275 patients were randomly allocated (1:1) to remdesivir or control (local standard of care, no placebo). For the study’s primary endpoint of in-hospital mortality, findings were similar to the preliminary results. Patients not ventilated who received remdesivir had lower mortality than those who did not; all those not ventilated (11.9% versus 13.5%; P=0.02) and patients not ventilated but on oxygen (14.6% versus 16.3%; P=0.03). There was no statistically significant difference in overall mortality, mortality of those already ventilated, or mortality in those not ventilated and not on oxygen. For all patients not ventilated initially, the rate of progression to ventilation was similar between both groups (14.1% versus 15.7%; P=0.04). However, when looking at a composite outcome of death or progression to ventilation, the remdesivir group had better outcomes (19.6% versus 22.5%; P=0.001). Comparing Solidarity to other trials, there were differences in how respiratory support was categorized (for example low flow versus high flow oxygen versus non-invasive ventilation). Three categories were defined: no oxygen; not ventilated but on oxygen; and ventilated. In meta-analysis, there was no difference in overall mortality or mortality in ventilated patients. There was an improvement in mortality in the combined non-ventilated subgroups (P=0.006).
Bottom line: Remdesivir improves mortality in hospitalized patients who are not already ventilated. The progression to ventilation benefit is only seen when combined with the outcome of mortality. More studies are needed to better understand how this mortality benefit may vary with different levels of oxygen support.
Citation: WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet. 2022;399(10339):1941-53.
Dr. Gibson is an assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine and staff physician in the department of hospital medicine and department of medical operations at the Cleveland Clinic, Cleveland.