Early administration of the antiparasitic drug ivermectin did not shorten the time to clinical improvement in 400 adults who were mildly ill with COVID-19, a clinical trial today in JAMA find.
Led by researchers from the Centro de Estudios and Infectologia Pediatrica in Cali, Colombia, the single-center, double-blind, randomized trial within the first 7 days used random sampling of coronavirus-positive patients to identify inpatients and outpatients with mild COVID-19 . after the onset of the symptom from 15 July to 30 November 2020.
The median time to symptom resolution was 10 days in the 200 patients receiving ivermectin at random for 5 days, compared with 12 days in 198 patients receiving 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% who received a placebo were symptom-free. Only 2% of patients in the ivermectin group and 3.5% in the placebo group experience a 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.
Increasing care, fever
There were no significant differences between the two groups in the proportion of patients who required more aggressive care (2% receiving ivermectin versus 5% receiving placebo; absolute difference, -3.05) or in the duration of time required escalated care wash. (median difference, 7 days).
There were also no significant differences in the ratios 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 or telemedicine visits.
Seventy-seven percent of the ivermectin group and 81.3% of the placebo group had side effects, with 7.5% of the former group and 2.5% of the latter group as a result. The most common side effect was headache (52% in the ivermectin group, 56% in the placebo group). Other symptoms were cough and faint odor and taste.
Two patients in each group developed multiorgan failure, which made it the most common serious side effect, although none of the cases were considered treatment-related. One patient who received placebo died.
The mean age of the participant was 37 years, 58% were women, 58.3% were outpatients and 79% had no underlying medical conditions.
Solid evidence for use is lacking
Cumulatively, the findings suggest that ivermectin does not significantly affect the course of early COVID-19, consistent with pharmacokinetic models showing that total and unbound plasma ivermectin levels do not reach the concentration leading to 50% 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 the treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.”
Laboratory 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 shows signs of antiviral activity early in the course of other types of infections. As a result, some countries have included the drug in their coronavirus treatment guidelines, which taxed the stock early in the pandemic, despite a lack of study in clinical trials.
“To our knowledge, preliminary reports of other randomized trials with ivermectin as treatment for COVID-19 with positive results have not yet been published in peer-reviewed journals,” the researchers wrote.