Ivermectin is ineffective in non-severe COVID-19 patients according to new study

By Tarun Sai LomteOct 25 2022Reviewed by Aimee Molineux

A recent study published in the Journal of American Medical Association (JAMA) evaluated the effect of ivermectin on time to recovery from coronavirus disease 2019 (COVID-19) in patients with mild to moderate disease.

Background

Novel antiviral drugs have been authorized for use in high-risk individuals in high-income countries. Still, their efficacy in vaccinated populations remains unknown, besides the limited global access to these drugs. Notwithstanding the advances in COVID-19 treatment, more therapies are required, especially in outpatient settings. Research on repurposed drugs has focused chiefly on the inpatient setting for treating severe illness.

Studies on repurposed drugs in outpatients have been limited by design limitations, small sample sizes, and variable results. Ivermectin is an antiparasitic drug used globally for strongyloidiasis and onchocerciasis that emerged as a potential repurposed drug for COVID-19 in 2020. Preliminary evidence suggested a possible therapeutic effect, particularly among inpatients. Dosing variability, study quality, and multiple article retractions have resulted in controversy.

About the study

In the present study, researchers assessed the effect of ivermectin on early mild/moderate COVID-19 in an ongoing, double-blind, placebo-controlled, and randomized trial. Recruitment into the trial began in June 2021 and is ongoing. Participants were recruited into the ivermectin group from June 23, 2021, until February 4, 2022, in the United States (US).

The eligibility criteria were age (30 or above), confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and two or more acute COVID-19 symptoms. Reported symptoms were fatigue, cough, fever, dyspnea, nausea, diarrhea, chills, body aches, sore throat, loss of smell/taste, nasal symptoms, and vomiting.

Exclusion criteria were hospitalization, use of the study drug in the past two weeks, and contraindication/allergy to the study drug. Participants were randomized using a random number generator. Ivermectin or a placebo was directly delivered to participants. They were instructed to take tablets for three days at approximately 400 μg/kg.

The primary outcome was time to sustained recovery, viz., absence of symptoms for three consecutive days. Time to recovery was the number of days from the first receipt of the study drug until the third successive symptom-free day. Secondary outcomes were hospitalization, urgent care visits, emergency department visits, or death by day 28.

Demographic information (race/ethnicity, concomitant medications, or medical history) was reported by participants at screening. Participants completed daily assessments and reported adverse events through the study portal. Assessments were designed to capture data on symptoms, severity, medications, and healthcare visits.

The time-to-event analysis was performed using proportional hazard regression. The primary endpoint analysis was a Bayesian proportional hazards model. A hazard ratio greater than one indicates therapeutic benefit. A posterior probability of benefit > 0.95 meant that the intervention was effective.

Findings

The ivermectin group had 817 participants, and the placebo cohort had 774. The mean age was 48; 59% of the participants were females, 81% were White individuals, 10% were Hispanic individuals, and 7% were Black individuals. In total, 47% of participants were double vaccinated. The median duration from symptom onset and study drug administration was six days.

The median time to recovery was 12 days for those in the ivermectin group and 13 days for the placebo group. The posterior probability of benefit on the primary outcome (time to recovery) was 0.91 between the two study arms, lower than the threshold of 0.95. Cases of hospitalization/death were fewer in both groups, 10 in the ivermectin arm and nine in the placebo group.

The secondary outcomes were similar between the ivermectin (3.9%) and placebo (3.6%) groups. The researchers did not find evidence of a different therapeutic effect with ivermectin for the timing of symptom onset to study drug receipt, body mass index, or vaccination status compared to the placebo group. Adverse events were similar and uncommon across both study arms. One participant who reported not taking the study drug experienced acute kidney injury.

Conclusions

Overall, in COVID-19 outpatients with mild or moderate illness, ivermectin use for three days at a dose of 400 μg/kg showed no significant improvement in the time to sustained recovery compared to those who received placebos. There was no therapeutic benefit in secondary clinical outcomes such as hospitalization, acute care visits, or deaths. These results do not support ivermectin use in COVID-19 patients with mild or moderate disease.