Remdesivir for coronavirus disease 2019 (COVID-19): a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials

Abstract

Background: In view of many unanswered clinical questions regarding treatment of COVID-19 with remdesivir, we systematically identified, critically appraised and summarized the findings from randomized controlled trials (RCTs) of remdesivir for COVID-19. Methods: We searched relevant databases/websites (up to September 2020) and selected English-language RCT publications of remdesivir for COVID-19. We conducted meta-analysis using an inverse variance, random-effects model in addition to trial sequential analysis (TSA) for the efficacy outcomes: all-cause mortality, viral burden and clinical progression. Safety outcomes were diarrhoea, nausea, and vomiting. We calculated the relative risk (RR) and 95% confidence interval (CI) for all outcomes. Statistical heterogeneity was calculated using the I 2 statistic. Results: We included five RCTs (7540 participants) from 7237 citations. Most (80%) were of an unclear to high risk of bias. There was no evidence of a significant improvement with remdesivir (100 mg, 10 days) regarding all-cause mortality (RR 0.94, CI 0.82–1.07; I 2 = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99–1.18; I 2 = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40–1.66; I 2 = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28–6.03; I 2 = 0%; 2 RCTs; 630 patients). TSA showed that the required information size was not reached for firm conclusions to be drawn. Conclusions and relevance: There is insufficient evidence to support the use of remdesivir for treatment of COVID-19. More high-quality RCTs are needed for a stronger evidence. Until then, remdesivir should remain an experimental drug for COVID-19.