Favipiravir for treating patients with novel coronavirus (COVID-19): protocol for a systematic review and meta-analysis of randomised clinical trials

  1. Morteza Arab-Zozani
  2. Soheil Hassanipour
  3. Djavad Ghoddoosi-Nejad

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Abstract

An outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was reported in Wuhan, China, in mid-December 2019, and declared a pandemic by the WHO on 11 March 2020. Due to the unknown nature of the disease and the lack of specific drugs, several potential treatments were used for patients. This systematic review and meta-analysis will evaluate studies of the effects of favipiravir in COVID-19 pneumonia.

Methods and analysis

We will search electronic databases including LitCovid hub, PubMed, Scopus, ISI Web of Sciences, Cochrane and Embase using keywords related to COVID-19 and favipiravir. We will search the reference lists of all included studies and reviews. We will also search for clinical trial registries, such as ClinicalTrials.gov, for the ongoing clinical trials. All randomised clinical trials investigating the safety and efficacy of favipiravir compared with other control groups for the treatment of patients with confirmed infection with SARS-CoV-2 will be included. Patients’ survival at the end of the treatment as well as the follow-up will be the primary outcome of the treatment, followed by the time and rate of the patient with a negative COVID-19 test. The desired secondary outcome will consist of a decreased rate of symptoms, proportion of intensive care unit (ICU) transfers, length of the hospital stay, ICU treatments, the quality of life and additional adverse events. Data synthesis will be conducted using CMA V.2. Two independent investigators will be screening titles, abstracts and full texts of included studies, based on eligibility criteria. These investigators will then independently extract the data and appraise the quality of said studies. All potential discrepancies will be resolved through consultation with the third reviewer. Statistical heterogeneity will be assessed using a standard I 2 test. A funnel plot, Egger’s test and Begg’s test will be used for detecting asymmetry to explore possible publication bias.

Ethics and dissemination

All findings of this systematic review and meta-analysis will help identify the safety and efficacy of favipiravir for patients with COVID-19. Given that the design of the study is a systematic review, there is no need to follow the code of ethics protocol. The results of this study will be published in a reputable journal.

PROSPERO registration number

CRD42020180032.

Article activity feed

  1. Version published to 10.1136/bmjopen-2020-039730
  2. ScreenIT

    SciScore for 10.1101/2020.04.27.20081471: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationThe data extraction form includes the following items; authors name, year of the publication, study design, study sample, country of origin, mean age of participants, gender, the severity of diseases, comorbidities, type of intervention and dose, control group, follow up, randomization, blinding, allocation concealment, primary and secondary outcomes, and adverse events.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Information sources and search strategy: Two independent reviewers (MA-Z and SH) will search electronic databases including PubMed, Scopus, ISI web of Sciences, Cochrane, Embase, LitCovid hub 13, and Scientific Information Database14 using keywords combination (MeSH term and free term), such as “2019 nCoV” OR 2019nCoV OR “2019 novel coronavirus” OR COVID-19 OR “new coronavirus” OR “novel coronavirus” OR “SARS CoV-2” OR (Wuhan AND coronavirus) OR “SARS-CoV” OR “2019-nCoV” OR “SARS-CoV-2” and Favipiravir OR Avigan.
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    We will search the reference lists of all included studies, reviews, and clinical trial registries, for an ongoing clinical trial (see Appendix 2 for the final proposed PubMed search strategy).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    We will assess the risk of bias of the included studies using Cochrane Collaboration criteria including seven items of selection bias (random sequence generation and allocation concealment), performance bias, detection bias, attrition bias, reporting bias, and other bias.
    Cochrane Collaboration
    suggested: None
    Data synthesis: Statistical analyses will be carried out using the RevMan software (version 5.3) or CMA (version 2).
    RevMan
    suggested: (RevMan, RRID:SCR_003581)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

  3. Version published to 10.1101/2020.04.27.20081471v1 on medRxiv