Early administration of the antiparasitic drug ivermectin did not significantly reduce the time to clinical improvement in 400 adults slightly ill with COVID-19, a clinical trial today JAMA finds.
Led by researchers from the Centro de Estudios en Infectologia Pediatrica in Cali, Colombia, the double-blind, randomized, single-center clinical trial used random sampling of positive coronavirus patients to identify inpatients and outpatients with mild COVID-19 in the first 7 days after onset symptoms from July 15 to November 30, 2020.
The mean 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 who received a placebo (interquartile range for both, 9 to 13 days; risk, 1.07).
Twenty-one days after starting treatment, 82% in the ivermectin group and 79% who received a placebo were asymptomatic. 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 eight point ordinal scale (absolute difference, -1.53). The odds ratio for clinical deterioration in those who received ivermectin versus placebo was 0.56.
Climbing 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 period of time that stepped care was needed (mean difference, 7 days).
Nor were there any significant differences in the proportions of patients with fever (absolute difference between ivermectin and placebo, -2.61) or in the duration of fever (absolute difference, -0.5 days). Ivermectin did not reduce visits to the emergency department or telemedicine.
Seventy-seven percent of the ivermectin group and 81.3% of the placebo group experienced adverse events, with 7.5% in the first group and 2.5% in the last 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 impaired cough and odor and taste.
Two patients in each group developed multiple organ failure, making it the most common serious adverse event, although none of the cases was considered treatment-related. One patient who received a placebo died.
The average age of the participants was 37 years, 58% were women, 58.3% were outpatients and 79% had no known underlying medical conditions.
Solid evidence for use is lacking
“Cumulatively, the results suggest that ivermectin does not significantly affect the course of the initial COVID-19, consistent with pharmacokinetic models that show that plasma levels of total and unbound ivermectin do not reach the concentration that results in 50% of viral inhibition, even at a dose level 10-fold higher than the approved dose “, concluded the authors.
“The results do not support the use of ivermectin for the treatment of mild COVID-19, although larger studies may be needed to understand the effects of ivermectin on other clinically relevant results.”
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 showed signs of antiviral activity early in the course of other types of infections. As a result, some countries have included the drug in their treatment guidelines for coronavirus, charging taxes at the start of the pandemic, despite the lack of studies in clinical trials.
“As far as we know, preliminary reports from other randomized clinical trials of ivermectin as a treatment for COVID-19 with positive results have not yet been published in peer-reviewed journals,” the researchers wrote.