Is ivermectin effective for treating COVID-19?

Ivermectin is Not Effective for COVID-19 Treatment

Ivermectin is not recommended for the treatment of COVID-19 in either hospitalized patients or outpatients, as current high-quality evidence shows no significant benefit for mortality, disease progression, or viral clearance. 1

Evidence Against Ivermectin Use in COVID-19

Recommendations from Clinical Guidelines

• The Infectious Diseases Society of America (IDSA) makes a conditional recommendation against ivermectin for hospitalized COVID-19 patients (very low certainty of evidence) and a strong recommendation against ivermectin for ambulatory COVID-19 patients (moderate certainty of evidence) 1

• Despite ivermectin's in vitro activity against SARS-CoV-2, the concentrations required to achieve antiviral effects are considerably higher than those achievable in human plasma and lung tissue at standard dosing 1

Key Clinical Outcomes

Mortality

• Treatment with ivermectin does not reduce mortality in COVID-19 patients (RR: 0.83; 95% CI: 0.50,1.37; high certainty of evidence) 1

• In hospitalized patients, the evidence failed to demonstrate a meaningful effect on mortality (RR: 0.54; 95% CI: 0.28,1.03; moderate certainty of evidence) 1

Disease Progression

• Ivermectin failed to demonstrate a beneficial effect on:
  • Hospitalization in outpatients (RR: 0.85; 95% CI: 0.65,1.11; moderate certainty of evidence) 1
  • Need for mechanical ventilation (RR: 0.40; 95% CI: 0.13,1.27; low certainty of evidence) 1
  • Symptom resolution (RR: 0.72; 95% CI: 0.44,1.17; moderate certainty of evidence) 1

Viral Clearance

• No significant effect on viral clearance at day seven in either hospitalized patients (RR: 1.21; 95% CI: 0.77,1.90; very low certainty of evidence) or outpatients (RR: 1.11; 95% CI: 0.85,1.44; very low certainty of evidence) 1

Recent High-Quality Evidence

• The PRINCIPLE trial (2024), a large multicenter, adaptive platform randomized controlled trial, found that while ivermectin showed a statistically significant reduction in time to recovery (median decrease of 2.06 days), the probability of a clinically meaningful effect was low (0.192) 2

• The IVERMILCO Study (2024), a multi-regional Phase III study in Japan and Thailand with 1,030 participants, found no statistically significant difference in time to symptom improvement between ivermectin and placebo groups (p = 0.61) 3

Safety Considerations

• While ivermectin is generally well-tolerated at doses used for parasitic infections, potential serious adverse events cannot be excluded in COVID-19 patients 1

• The risk of serious adverse events in hospitalized patients treated with ivermectin versus no ivermectin showed a concerning trend (RR: 3.10; 95% CI: 0.54,17.89; moderate certainty of evidence), though the confidence interval is wide 1

Common Pitfalls and Caveats

• Early enthusiasm for ivermectin was based largely on in vitro studies and non-peer-reviewed trials, which subsequent higher-quality research has not supported 4

• Some early studies had significant methodological limitations, including:

  • Inadequate randomization methods (e.g., allocation based on odd/even days or registration numbers) 1
  • Lack of blinding of study personnel 1
  • Studies not prospectively registered according to WHO guidelines 5

• The Cochrane review (2022) excluded seven previously included trials due to lack of prospective registration or non-randomization 5

Clinical Decision Algorithm

1. For patients with COVID-19 (both hospitalized and outpatient):

   • Do NOT prescribe ivermectin for COVID-19 treatment 1

2. For patients requesting ivermectin:

   • Explain that high-quality evidence shows no benefit for mortality, hospitalization, or viral clearance 1
   • Discuss that major medical societies and guidelines recommend against its use 1
   • Consider offering proven COVID-19 therapies appropriate to the patient's condition instead 1

3. For patients with concurrent parasitic infections who also have COVID-19:

   • Treat the parasitic infection according to standard guidelines
   • Do not expect ivermectin to provide additional benefit for COVID-19 symptoms 1

In conclusion, based on the most recent and highest quality evidence, ivermectin should not be used for the treatment of COVID-19 outside of clinical trials, as it has not demonstrated meaningful clinical benefits for mortality, disease progression, or viral clearance.