Tools for Practice


#297 Opening a can of helminths: Ivermectin for COVID-19


CLINICAL QUESTION
Does ivermectin improve clinical outcomes in COVID-19?

BOTTOM LINE
The best available evidence does not show that ivermectin improves clinically important outcomes in COVID-19. Use in COVID-19 is discouraged.


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EVIDENCE
Focusing on quality randomized controlled trials (RCTs) and systematic reviews reporting patient-oriented outcomes and published in peer reviewed journals.
  • Two large, well designed, double-blind, RCTs:
    • 400 patients with mild COVID-19 (at home or hospitalized without oxygen support) randomized to ivermectin or placebo for 5 days:1
      • Time to symptom resolution:
        • Not statistically different: 10 days ivermectin, 12 days placebo.
    • 501 out-patients randomized to ivermectin or placebo for 2 days:2
      • COVID-19 related hospitalization:
        • Not statistically different: Ivermectin 5.6% versus 8.4% placebo.
  • High-quality living meta-analysis found no statistically significant impact of ivermectin on any clinical outcome.3
    • 19 RCTs with 2740 patients (outpatients and inpatients); primarily reported on surrogate outcomes (example viral load).
    • Clinical outcomes in outpatients at day 28:
      • Clinical improvement: 2 trials (526 patients): No difference.
      • All-cause mortality: 4 trials (1255 patients): No difference.
    • Formally published systematic review found similar.4
Context
  • Most ivermectin trials are not published in peer reviewed journals, have small numbers of participants, are at high risk of bias, or only report on surrogate markers.3
    • One oft-cited “meta-analysis” which reported a benefit had no authors listed, included cohort studies, and had questionable conclusions regarding study quality.5
    • The study with the largest reported mortality effect (only available in pre-print), was retracted due to data integrity issues.6,7
  • Of >14,000 COVID-19 pre-prints:
    • Only ~30% are published in peer reviewed journals one year later.8
    • Pre-print results and conclusions can change substantially when published as peer reviewed publication:
      • Example COLCORONA trial: Same results, different conclusions.
        • Preprint: “colchicine reduces the composite rate of death or hospitalization”.9
        • Publication: “effect of colchicine on COVID-19-related clinical events was not statistically significant”.10
  • Despite the evidence, animal feed stores inundated with requests for ivermectin.11
  • Poison control centers report increased calls for ivermectin toxicity.12
    • Toxicity symptoms may include nausea/vomiting, abdominal pain, diarrhea, headache, blurred vision, dizziness, and seizures.12
September 7, 2021

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Author(s):

  • Michael R Kolber MD CCFP MSc
  • Tony Nickonchuk BScPharm

1. López-Medina E, López P, Hurtado IC, et al. JAMA 2021; 325(14):1426-35. doi:10.1001/jama.2021.3071

2. 2. Vallejos J, Zoni R, Aguirre MG, et al. BMC Inf Dis. 2021: 635(21).

3. COVID-NMA Consortium. (2020). RCT studies on preventive measures and treatments for COVID-19:Ivermectin. Available at: https://covid-nma.com. Accessed August 9, 2021.

4. Popp M, Stegemann M, Metzendorf M-I, et al. Cochrane Database of Systematic Reviews 2021, Issue 7. Art. No.: CD015017. DOI: 10.1002/14651858.CD015017.pub2.

5. No authors. Ivermectin for COVID-19: real-time meta-analysis of 61 studies. Available at: http://ivmmeta.com. Accessed August 9, 2021.

6. Elgazzar A, Eltaweel A, Abo Youssef S, et al. [Retracted] Research Square. doi: https://doi.org/10.21203/rs.3.rs-100956/v3.

7. Reardon S. Nature. 2021 Aug 2. Available at: https://www.nature.com/articles/d41586-021-02081-w. Accessed August 9, 2021.

8. Authors’ calculations using medrxivr R package. Available at: https://cran.r-project.org/web/packages/medrxivr/index.html. Accessed August 12, 2021.

9. Tardif JC, Bouabdallaoui N, L’Allier PL, et al. MedRxiv 2021. 01.26.21250494; doi: https://doi.org/10.1101/2021.01.26.21250494.

10. Tardif JC, Bouabdallaoui N, L’Allier PL, et al. Lancet Respir Med. 2021; 9:924-32.

11. CBC news Aug 30, 2021. Available at: https://www.cbc.ca/news/canada/calgary/ivermectin-alberta-covid-1.6157200

12. Centers for Disease Control (CDC) Advisory. Available at: https://emergency.cdc.gov/han/2021/han00449.asp. Accessed Aug 30, 2021.

Authors do not have any conflicts of interest to declare.