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


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

BOTTOM LINE
RÉSULTAT FINAL
 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
DONNÉES PROBANTES
 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    • The study with the largest reported mortality effect (only available in pre-print), was retracted due to data integrity issues.6,7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

Nancy Robson September 17, 2021

Interesting

Martin Withers January 1, 2022

Good update

Sanjiv Anand January 15, 2022

No benefit from use of ivermectin in treatment of Covid

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Author(s)
Auteur(s)
  • Tony Nickonchuk BScPharm
  • Michael R Kolber MD CCFP MSc

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.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.