Early administration of the antiparasitic drug ivermectin didn't significantly shorten time to clinical improvement in 400 adults mildly ill with COVID-19, a clinical trial today in JAMA finds.
Led by researchers from the Centro de Estudios en Infectologia Pediatrica in Cali, Colombia, the single-center, double-blind, randomized trial used random sampling of coronavirus-positive patients to identify inpatients and outpatients with mild COVID-19 within the first 7 days after symptom onset from Jul 15 to Nov 30, 2020.
Median time to symptom resolution was 10 days in the 200 patients randomly assigned to receive ivermectin daily for 5 days, compared with 12 days in 198 patients receiving a placebo (interquartile range for both, 9 to 13 days; hazard ratio, 1.07).
Twenty-one days after starting treatment, 82% in the ivermectin group and 79% receiving a placebo were symptom-free. Only 2% of patients in the ivermectin group and 3.5% in the placebo group experienced clinical deterioration of at least two points on an ordinal eight-point scale (absolute difference, -1.53). The odds ratio for clinical deterioration in those receiving ivermectin versus placebo was 0.56.
Escalation of care, fever
There were no significant differences between the two groups in the proportion of patients who needed more aggressive care (2% who received ivermectin vs 5% who received placebo; absolute difference, -3.05) or in the length of time that the escalated care was needed (median difference, 7 days).
Nor were there significant differences in the proportions of patients with fever (absolute difference between ivermectin and placebo, -2.61) or in the length of the fever (absolute difference, -0.5 days). Ivermectin did not reduce emergency department or telemedicine visits.
Seventy-seven percent of the ivermectin group and 81.3% of the placebo group had adverse events, with 7.5% of the former group and 2.5% of the latter group discontinuing treatment as a result. The most common side effect was headache (52% in the ivermectin group, 56% in the placebo group). Other symptoms included cough and impaired smell and taste.
Two patients in each group developed multiorgan failure, making it the most common serious adverse event, although none of the cases were considered treatment-related. One patient who received placebo died.
Median participant age was 37 years, 58% were women, 58.3% were outpatients, and 79% had no known underlying medical conditions.
Solid evidence for use lacking
"Cumulatively, the findings suggest that ivermectin does not significantly affect the course of early COVID-19, consistent with pharmacokinetic models showing that plasma total and unbound ivermectin levels do not reach the concentration resulting in 50% of viral inhibition even for a dose level 10-times higher than the approved dose," the authors concluded.
"The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes."
Lab and animal studies have suggested that ivermectin has activity against SARS-CoV-2, the virus that causes COVID-19, the authors noted, adding that the drug showed signs of antiviral activity early in the course of other types of infections. As a result, some countries included the drug in their coronavirus treatment guidelines, taxing supplies early in the pandemic, despite a lack of study in clinical trials.
"To our knowledge, preliminary reports of other randomized trials of ivermectin as treatment for COVID-19 with positive results have not yet been published in peer-reviewed journals," the researchers wrote.