Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis

  1. Leonard Chiu
  2. Max Shen
  3. Chun-Han Lo
  4. Nicholas Chiu
  5. Austin Chen
  6. Hyun Joon Shin
  7. Elizabeth Horn Prsic
  8. Chin Hur
  9. Ronald Chow
  10. Benjamin Lebwohl

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.

Methods

Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.

Results

Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death—HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.

Conclusion

Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

Article activity feed

  1. Version published to 10.1371/journal.pone.0259514
  2. ScreenIT

    SciScore for 10.1101/2021.03.14.21253537: (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 variableFurthermore, we noted sample size, study design, patient population, mean/median age, percentage male, percentage famotidine users, and adjusted confounding variables.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy: Five databases, namely Ovid Medline, Embase, Cochrane Central Register of Controlled
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Risk of Bias Assessment: The Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool, developed by the Cochrane Bias Methods Group, was used to assess risk of bias for all observational studies included in this meta-analysis (21).
    Cochrane Bias
    suggested: (Robot Reviewer, RRID:SCR_018961)

    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:
    There are several limitations to this study. First, the strength of our findings is limited by the quality of included studies as is the case for all systematic reviews and meta-analyses. To account for confounding, this meta-analysis contains only observational data that reported adjusted relative risks. Although all the included observational studies had some concern for risk of bias, they employed propensity score matching to minimize selection bias. Additionally, only one study explicitly included patients with COVID-19 treated with famotidine before and during hospitalization (15). Other studies may have included patients who also used famotidine before hospitalization as they may have used as continuation of home use—an assumption made by Freedberg et al. Furthermore, while we employed a random effects model for our analysis, the heterogeneity is high. Lastly, there are subtle yet meaningful differences in the definition of composite outcome across the four studies, thereby allowing for potential bias when calculating aggregate ORs/HRs. Given the paucity of data reported in the literature, the directionality of these results should only be used for hypothesis-generation rather than clinical decision making. In conclusion, this meta-analysis suggests that famotidine does not reduce the risk of mortality in individuals hospitalized with COVID-19. Similarly, there was a point estimate suggesting a decreased risk of the composite outcome of death, intubation, and/or use of ...

    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 10.1101/2021.03.14.21253537 on medRxiv