A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19

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Abstract

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  1. SciScore for 10.1101/2021.04.19.21255441: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Each participant or his/her guardian was provided written informed consent prior to the initiation of any study procedures.
    IRB: The central institutional review board (IRB) or a local IRB at each center approved the protocol.
    Sex as a biological variableIn addition, females of childbearing potential who were either pregnant or sexually active and not using birth control were excluded.
    RandomizationStudy design and subjects: This was a multicenter randomized controlled trial conducted in 36 centers in the U.S. and Puerto Rico.
    BlindingThe performance characteristics of the FLU-PRO instrument and appropriateness of background levels in subjects with SARS-CoV-2 infection were confirmed by blinded analysis of diary data for this study after database lock and prior to unblinding.
    Power AnalysisA sample size of 312 subjects (156 per group) was calculated to provide 90% power to detect a statistically significant difference in the survival distributions between the nitazoxanide and placebo groups (two-sided α =0.05).
    Cell Line AuthenticationAuthentication: The FLU-PRO instrument has been validated for use in subjects with influenza and influenza-like illnesses20.

    Table 2: Resources

    Antibodies
    SentencesResources
    Blood samples collected at baseline and day 22 were tested for quantitative anti-SARS-CoV-2 antibodies.
    anti-SARS-CoV-2
    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:
    Subjects were enrolled based upon symptoms to ensure early treatment, avoiding limitations associated with the availability and delays in diagnostic testing, and 379 subjects with confirmed SARS-CoV-2 infection were analyzed for effectiveness. The trial was appropriately blinded, and subjects were closely followed for 28 days. Endpoints developed early during the course of the pandemic were objective and well-defined, and rigorous data collection procedures were employed. Treatment with nitazoxanide 600 mg orally twice daily for five days was associated with an 85% reduction in the rate of progression to severe illness (the key secondary endpoint). All severe illnesses occurred in the subgroup of subjects at high risk of severe illness according to CDC criteria, and all occurred between study days 3 and 10. Treatment with nitazoxanide was also associated with a 79% reduction in the rate of hospitalization. While the overall number of events is low, the number are consistent with and compare favorably to those used to support approval of monoclonal antibodies for use under Emergency Use Authorization in the United States3,4,21,22. Notably, severe illnesses were associated with high viral loads in nasopharyngeal swabs collected at either the baseline visit or day 4. Similar observations have been reported by others21,23. In the analysis of the primary endpoint, treatment with nitazoxanide was not associated with a reduction of TSR (a measure of the duration of meaningful sympto...

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

    IdentifierStatusTitle
    NCT04486313CompletedTrial to Evaluate Efficacy and Safety of Nitazoxanide in the…


    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.