Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis of the Chinese Lancet trial with the NIH trial

  1. Paul Elias Alexander
  2. Joshua Piticaru
  3. Kimberley Lewis
  4. Komal Aryal
  5. Priya Thomas
  6. Wojciech Szczeklik
  7. Jakub Fronczek
  8. Kamil Polok
  9. Waleed Alhazzani
  10. Manoj Mammen

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Abstract

Background

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use.

Methods

A rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study.

Results

Two RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96).

Conclusion

In this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.23.20110932: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy and study selection: MEDLINE and EMBASE electronic databases were searched from January 1st, 2020, to May 22nd, 2020, using a mix of keywords such as ‘COVID-19’ and ‘remdesivir along with any relevant variants.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    PubMed was also searched daily during this period to rapidly assess any emerging publications.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Evidence was considered from additional sources, including Google Scholar and online preprint servers, that pre-publish studies not yet having completed the peer-review process.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our analysis of the available literature had significant limitations, including the paucity of studies available for analysis. The research evidence on the benefits of remdesivir in COVID-19 is however, in our judgement, based on two rigorous multicenter trials. Additionally, there was significant heterogeneity in the time to clinical improvement, which could be due to the location of the studies and the differences in standard of care between the studies that were conducted at different periods in the context of the evolving evidence landscape during the pandemic. Timing of initiation of remdesivir may also impact clinical outcomes, with patients with more severe disease being less likely to survive as seen in the ACTT-1 subgroups, however we were unable to pool data according to these subgroups. Due to the public health emergency of the COVID-19 pandemic, there likely will not be any additional randomized, placebo-controlled, double-blind trial to determine remdesivir’s efficacy in patients with COVID-19, and instead, it would be incorporated into standard of care. In addition, remdesivir appears to reduce the time to clinical improvement and the number of serious adverse events and can ameliorate the conditions at many overwhelmed hospitals facing the pandemic patient surges. The primary concern present in the context of the current crisis with continued lack of a viable treatment option in patients suffering from Sars-CoV-2 life-threatening respiratory failure, indeed per...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.05.23.20110932v1 on medRxiv