Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis

  1. Alex Castañeda-Sabogal
  2. Diego Chambergo-Michilot
  3. Carlos J. Toro-Huamanchumo
  4. Christian Silva-Rengifo
  5. José Gonzales-Zamora
  6. Joshuan J. Barboza

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

To assess the outcomes of ivermectin in ambulatory and hospitalized patients with COVID-19.

Methods

Five databases and websites for preprints were searched until January 2021 for randomized controlled trials (RCTs) and retrospective cohorts assessing ivermectin versus control in ambulatory and hospitalized participants. The primary outcome was overall mortality. Secondary outcome was recovered patients. For meta-analysis, random-effects and inverse variance meta-analyses with logarithmic transformation were performed. ROBINS-I for cohort studies, and the Cochrane Risk of Bias 2.0 tool for trials were used. The strength of evidence was assessed using GRADE.

Results

After the selection, twelve studies (five retrospective cohort studies, six randomized clinical trials and one case series), were included. In total, 7412 participants were reported, the mean age was 47.5 (SD 9.5) years, and 4283 (58%) were male. Ivermectin was not associated with reduced mortality (logRR: 0.89, 95% CI 0.09 to 1.70, p = 0.04, I 2 = 84.7%), or reduced patient recovery (logRR 5.52, 95% CI -24.36 to 35.4, p = 0.51, I 2 = 92.6%). All studies had a high risk of bias, and showed a very low certainty of the evidence.

Conclusions

There insufficient certainty and quality of evidence to recommend the use of ivermectin to prevent or treat ambulatory or hospitalized patients with COVID-19.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.01.26.21250420: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: No ethics committee approval was required.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data sources: We searched PubMed, Scopus, Web of Science, Ovid-Medline, Embase, websites for preprints/preproofs (“Other sources” ; https://www.medrxiv.org, https://preprints.scielo.org/index.php/scielo, https://www.biorxiv.org, https://arxiv.org), websites for protocols of clinical trials (https://clinicaltrials.gov).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    https://clinicaltrials.gov
    suggested: (ClinicalTrials.gov, RRID:SCR_002309)
    Risk of bias assessment: Two investigators (JJB, DCM) independently assessed the risk of bias by using the ROBINS-I (Risk Of Bias In Non-Randomized Studies of Interventions) tool (8) for cohort studies and the Cochrane Risk of Bias 2.0 tool (9) for trials; disagreements were resolved by discussion with a third investigator (ACS).
    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:

    One of the limitations of the study conducted by Padhy et al. is that the overall effect of ivermectin on mortality was analyzed without considering the reported effect measure. Furthermore, the analysis was performed without transforming the individual effect (from OR to LogOR, for example), thus the OR reported was overestimated. In another systematic review with networked meta-analysis, the effects of ivermectin on mortality were analyzed, and only two studies were included. The authors reported a very close statistical significance in terms of association of ivermectin with lower mortality (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005); however, they pointed out that these data had very low certainty of evidence (31). Despite the small amount of highly biased evidence that has been published supporting the efficacy of ivermectin, the specific human dose has not been established. Bray et al. evaluated in vitro whether an ivermectin concentration of 0.1 uM (instead of 5 uM) can inhibit SARS-Cov-2 (32). In clinical studies, the dose has ranged from 120 uM/kg to 200 uM/kg per dose in the intramuscular or oral form (33, 34). However, high doses for humans have not been approved (https://www.fda.gov/animal-veterinary/product-safety-information/faq-covid-19-and-ivermectin-intended-animals). It is important to know that testing the efficacy of ivermectin in human clinical trials or observational study requires a previous evaluation in a dose-response trial, applying low dose (with les...

    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 scite Reference Check: We found no unreliable references.

    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 10.1101/2021.01.26.21250420v1 on medRxiv