Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand

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Abstract

Favipiravir is a broad-spectrum oral antiviral agent that shows in vitro activity against SARS-CoV-2. Presently, data on the real-world effectiveness and optimal dosage of favipiravir for treating COVID-19 are limited. We conducted a retrospective observational study of hospitalized adult patients with COVID-19 at five tertiary care hospitals in Thailand. We reviewed patient charts to obtain all necessary data. Among 247 COVID-19 patients, 63 (23.0%) received ≥1 dose of favipiravir. Of these 63 patients, 61.9% were male with a median age of 48 years (range 22–85 years), 27.0% required an O2 nasal cannula, 9.5% required non-invasive ventilation and/or high-flow O2 therapy, and 6.4% required invasive mechanical ventilation and/or ECMO. The median baseline NEWS2 score was 5 (0–16). The Day-7 clinical improvement rate [95%CI] was 66.7% [53.7–78.0%] in all patients, 92.5% [75.7–99.1%] in patients who did not require O2 supplementation, and 47.2% [0.4–64.5%] in patients who required O2 supplementation. No life-threatening adverse events were identified. The 28-day mortality rate was 4.8%. A multivariate analysis revealed three poor prognostic factors for Day-7 clinical improvement (odds ratio (95%CI); p-value): older age (0.94 (0.89–0.99); p = 0.04), a higher baseline NEWS2 score (0.64 (0.47–0.88); p = 0.006), and a lower favipiravir loading dose (≤45 mg/kg/day) (0.04 (0.005–0.4); p = 0.006). In conclusion, our study reports the promising effectiveness of favipiravir for treating COVID-19 patients. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir (≤45 mg/kg/day) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the optimal dose and the optimal timing of drug initiation for favipiravir should be performed.

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  1. SciScore for 10.1101/2020.06.24.20133249: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: The study protocol was approved with a waiver of informed consent by the institutional review boards of all involved hospitals.
    IRB: The study protocol was approved with a waiver of informed consent by the institutional review boards of all involved hospitals.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All calculations were performed using STATA version 14.1
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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:
    Our study also has some limitations. First, the retrospective design resulted in a significant amount of missing data, especially for laboratory values. To resolve this issue, when performing the multivariate analysis, missing data was replaced by the mean value of a given variable. Second, majority of our patients also received chloroquine-based agent and protease inhibitors. Therefore, the good treatment response among our patients may be the synergistic results of triple combination of favipiravir, chloroquine-based agent and protease inhibitors. Furthermore, a high rate (54.0%) of diarrhea of the patients having favipiravir was probably related to protease inhibitor rather than favipiravir. Third, a sample size of 63 patients with COVID-19 pneumonia is not large enough to detect other associated factors with a low prevalence. Lastly, the generalizability of our findings may be an issue. Given that the study was conducted in tertiary care hospitals in Thailand, results may not be applicable to primary or secondary care settings or to COVID-19 patients in other countries. In conclusion, our study reports the promising effectiveness of favipiravir for treating COVID-19 patients in a tertiary care hospital setting. No life-threatening adverse events were identified. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir (≤45 MKD) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the ...

    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.
    • 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.