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

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 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; = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99-1.18; = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40-1.66; = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28-6.03; = 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.