A systematic review and meta-analysis of randomized controlled trials with trial sequence analysis of remdesivir for COVID-19 treatment.

Remdesivir is one of the proposed therapies for the corona virus disease 2019 (COVID-19). To assess the effect of remdesivir on mortality, need for invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO), time to clinical improvement, and significant adverse effects. The study protocol was prospectively registered with The International Prospective Register of Systematic Reviews (Registration #CRD42021283221). Randomized controlled trials (RCTs) published in English detailing use of remdesivir in hospitalized patients with COVID-19 were included. Primary outcome was in hospital mortality among patients receiving remdesivir. Secondary outcomes were need for IMV and ECMO, time to clinical recovery, and significant adverse effects associated with remdesivir. Odds ratios (ORs) of worse outcome with 95% confidence interval (CI) in a forest plot were used to show the results of random effects meta-analysis. Remdesivir and placebo had similar in hospital mortality in the pooled analysis of five RCTs (OR: 0.93, 95% CI: 0.82-1.06). The remdesivir group needed less IMV/ECMO (OR: 0.59, 95% CI: 0.46-0.76) and recovered 1.06 days faster than placebo. Remdesivir did not affect transaminitis or renal damage. Trial sequence analysis showed that death has not reached the number of instances needed to predict futility. This meta-analysis shows that remdesivir therapy for COVID-19 is not associated with a mortality benefit. However, there is significant reduction in the need for IMV/ECMO.