Impact of remdesivir on 28 day mortality in hospitalized patients with COVID-19: February 2021 Meta-analysis

  1. Robert Robinson
  2. Vidhya Prakash
  3. Raad Al Tamimi
  4. Nour Albast
  5. Basma Al-Bast
  6. Elizabeth Wieland
  7. Carlos Garcia

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Abstract

Background

The COVID-19 pandemic has stimulated worldwide investigation into a myriad of potential therapeutic agents, including antivirals such as remdesivir. The first RCT reporting results on the impact of remdesivir on COVID-19 in a peer reviewed journal was the ACTT-1 trial published in November, 2020. The ACTT-1 trial showed more rapid clinical improvement and a reduced risk of 28-day mortality in patients who received remdesivir.

This study is a meta-analysis of peer reviewed RCTs aims to estimate the association of remdesivir therapy compared to the usual care or placebo on all-cause mortality in hospitalized patients with COVID-19. Software based tools to accelerate the analysis process.

Methods

Meta-analysis of peer reviewed RCTs comparing remdesivir to usual care or placebo. The protocol for this meta-analysis was registered and published in the PROSPERO database (CRD42021229985) on February 5, 2021.

Results

Four English language RCTs were identified, including data from 7,333 hospitalized patients worldwide using remdesivir in COVID-19 positive patients.

Meta-analysis of all identified RCTs showed no difference in survival in patients who received remdesivir therapy compared to usual care or placebo. The random effects meta-analysis has a summary odd ratio is 0.89 (95% CI 0.65-1.21, p = 0.30). Considerable variability in the severity of illness is noted with the rates of IMV at the time of randomization ranging from 0% to 27%.

Conclusions

This meta-analysis of randomized controlled trials published in peer-reviewed literature by February 1, 2021 did not show reduced mortality in hospitalized patients with COVID-19 who received remdesivir. Further research is needed to clarify the role of remdesivir therapy in the management of COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.04.21252903: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationThe results of these searches were exported and filtered via the RobotSearch tool by Vortext Systems to identify randomized controlled trials.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Identification of trials: Trials were identified by searching MEDLINE using the search terms COVID-19 and remdesivir.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    12 The filtered results were reviewed for inclusion criteria and evaluated for bias via the RobotReviewer tool that applies the Cochrane Risk of Bias (RoB) tool to the full text of articles.
    Cochrane Risk of Bias
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study has several important limitations. The focus on English language publication in peer reviewed literature may under-represent the full spectrum of research in this rapidly evolving field. Remarkably, these 4 trials were conducted and published within 9 months of the World Health Organization declaration of the COVID-19 pandemic on March 11, 2020. The literature search and assessment methods used for this study is computer assisted, which differs from traditional meta-analysis techniques that are labor and time consuming. This strategy has the potential to introduce bias in the identification of RCTs. However, this methodology did produce similar results to other systematic reviews and meta-analyses on the same topic.17

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04280705CompletedAdaptive COVID-19 Treatment Trial (ACTT)
    NCT04257656TerminatedA Trial of Remdesivir in Adults With Severe COVID-19
    NCT04315948Active, not recruitingTrial of Treatments for COVID-19 in Hospitalized Adults

    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.
    • No protocol registration statement was detected.

    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 10.1101/2021.03.04.21252903 on medRxiv