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:

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

Transparency

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conceptualization (GNO); Methodology (GNO & RR); Data acquisition (GNO, VKR, OLTL, & NA); Formal analysis (GNO & RR); Validation (GNO & RR); Draft manuscript (GNO); Manuscript revisions (GNO, VKR, OLTL, NA & RR); Final approval for submission (GNO, VKR, OLTL, NA & RR); Accountability (GNO, VKR, OLTL, NA & RR); Principal investigator (GNO)

Acknowledgements

The authors would like to thank Maureen Babb (Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, Manitoba, Canada) for peer reviewing the Embase search strategy, and Leslie Copstein and Amenah Al-Juboori (George and Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada) for their contributions to our previous systematic review on this topic.

Additional information

Funding

This paper was not funded.