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

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Infect Dis (Lond)


. 2021 May 11;1-9.
doi: 10.1080/23744235.2021.1923799. Online ahead of print.
Remdesivir for coronavirus disease 2019 (COVID-19): a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials


George N Okoli ¹ , Rasheda Rabbani ^{1 2} , Leslie Copstein ¹ , Amenah Al-Juboori ¹ , Nicole Askin ³ , Ahmed M Abou-Setta ^{1 2}



Affiliations

• PMID: 33974479
• DOI: 10.1080/23744235.2021.1923799

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 I² 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; I² = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99-1.18; I² = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40-1.66; I² = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28-6.03; I² = 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.

Keywords: COVID-19; Remdesivir; efficacy; randomized controlled trials; safety; systematic review.