Ivermectin Efficacy on Disease Progression among Adult Patients with Mild to Moderate COVID-19

JAMA Internal Medicine

Ivermectin treatment during early illness does not prevent progression to severe disease for high-risk patients with mild-to-moderate COVID-19, according to a study published online Feb. 18 in JAMA Internal Medicine.

An in vitro study demonstrated inhibitory effects of ivermectin against SARS-CoV-2. Although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.

In 2021, 2 randomized clinical trials from Colombia and Argentina found no significant effect of ivermectin on symptom resolution and hospitalization rates for patients with COVID-19.

Ivermectin is widely prescribed for COVID-19, contrary to the World Health Organization (WHO) recommendation to restrict use of the drug to clinical trials. In the present randomized clinical trial, authors studied the efficacy of ivermectin for preventing progression to severe disease among high-risk patients with COVID-19 in Malaysia.

Key Points

Question: Does adding ivermectin, an inexpensive and widely available antiparasitic drug, to the standard of care reduce the risk of severe disease in patients with COVID-19 and comorbidities?

Findings: In this open-label randomized clinical trial of high-risk patients with COVID-19 in Malaysia, a 5-day course of oral ivermectin administered during the first week of illness did not reduce the risk of developing severe disease compared with standard of care alone.

Meaning: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.

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TAKE-HOME MESSAGE

This multicenter open-label randomized clinical trial examined the use of oral ivermectin in preventing high-risk adult patients with mild to moderate COVID-19 infection from progressing to severe disease.

A total of 490 hospitalized patients were randomized to receive ivermectin and standard of care or standard of care alone. There was no statistically significant difference in rates of progression to severe disease, mechanical ventilation, ICU admission, or 28-day in-hospital death between the two groups.

Prior studies on the use of ivermectin in patients with mild to moderate COVID-19 infection have shown no substantial benefit largely in outpatient populations.

This study adds to available evidence suggesting that ivermectin does not reduce the risk of COVID-19 progression to severe disease across populations including hospitalized patients with underlying comorbidities.

No impact on progression to severe disease seen for high-risk patients with mild-to-moderate disease receiving ivermectin during early illness.

At present, repurposed anti-inflammatory drugs (dexamethasone, tocilizumab, and sarilumab), monoclonal antibodies, and antivirals (remdesivir, molnupiravir, and nirmatrelvir/ritonavir) have demonstrated treatment benefits at different stages of COVID-19.

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Abstract

Importance

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed.

Objective

To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19.

Design, Setting, and Participants

The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease.

Interventions

Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care or standard of care alone. The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging.

Main Outcomes and Measures

The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events.

Results

Among 490 patients included in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease. For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%), intensive care unit admission in 6 (2.4%) vs 8 (3.2%), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group).

Conclusions and Relevance

In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.