Update on efficacy of the approved remdesivir regimen for treatment of COVID-19: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials

Abstract

Background: Efficacy of remdesivir for COVID-19 remains unclear. We updated our published systematic review to better inform on the use of remdesivir for COVID-19.

Methods: We searched for randomized controlled trials (RCTs) among hospitalized COVID-19 patients. Meta-analysis was conducted using an inverse variance, random-effects model, presenting relative risk (RR) or mean difference (MD) and their associated 95% confidence intervals (CIs). Statistical heterogeneity was calculated using the I² statistic. In addition, we conducted trial sequential analysis (TSA). Outcomes with additional data were clinical progression, hospitalization days, and all-cause mortality.

Results: We included nine RCTs (12,876 individuals). Three trials each were of a low, unclear, and a high risk of bias. Compared with no treatment/placebo, remdesivir (100 mg daily, over 10 days) significantly improved clinical progression (RR 1.06, CI 1.02-1.11), but did not significantly reduce hospitalization days (MD -0.48, CI -2.18-1.21) and all-cause mortality (RR 0.92, CI 0.84-1.01). TSA suggested that further information is not required to conclude on the efficacy of remdesivir in improving clinical progression, and that, while more information is required for hospitalization days and all-cause mortality, further RCTs to prove fewer hospitalization days may be futile, as efficacy of remdesivir for this outcome is unlikely.

Conclusions: Remdesivir appeared promising for COVID-19, but there is insufficient evidence of its efficacy. High quality RCTs are needed for a stronger evidence base.

Keywords: COVID-19; Remdesivir; efficacy; hospitalized patients; laboratory-confirmed infection; meta-analysis; randomized controlled trials; safety; systematic review; trial sequential analysis.