Ivermectin not superior to placebo in mild COVID-19

Early treatment with single- or double-dose ivermectin is no better than placebo in avoiding progression to hospitalization and in improving symptoms in mild COVID-19, results of a study have shown.

“[I]vermectin early treatment, even using a double dose, was not superior to the placebo in preventing progression to hospitalization and achieving resolution of symptoms in mild COVID-19,” said the researchers, led by Alireza Mirahmadizadeh from Shiraz University of Medical Sciences, Shiraz, Iran.

A multi-arm randomized clinical trial was conducted between 9 April 2021 and 20 May 2021, involving a total of 393 patients with RT-PCR‒confirmed COVID-19 infection and mild symptoms. Participants were randomly assigned to receive single-dose ivermectin (12 mg), double-dose ivermectin (24 mg), or placebo. Need for hospitalization was the primary outcome.

No significant difference was observed in the number of patients who required hospitalization between placebo and single-dose ivermectin groups (absolute difference in proportions, ‒2.3, 95 percent confidence interval [CI], ‒8.5 to 4.1) and between placebo and double-dose ivermectin groups (absolute difference, ‒3.9, 95 percent CI, ‒9.8 to 2.2). [Respirology 2022;27:758-766]

Likewise, no statistical differences were seen in the odds of differences in mean change in severity score between single-dose ivermectin and placebo groups (odds ratio [OR]_difference, 1.005, 95 percent CI, 0.972‒1.040; p=0.762) and double-dose ivermectin and placebo (OR_difference, 1.010, 95 percent CI, 0.974‒1.046; p=0.598).

Six adverse events were reported, including mild dermatitis, tachycardia, and hypertension, but none of them were serious and required extra action.

“An important finding of our trial is the lack of clinical benefit from doubling the dose of ivermectin. This was also reported by several similar trials, even with higher than standard doses of ivermectin administered for a longer duration (ie, 5 consecutive days),” the researchers said. [Viruses 2021;13:989; JAMA 2021;325:1426-1435; Int J Antimicrob Agents 2022;59:106516]

“These studies were heterogenous with regard to definition of outcomes, assessment tools, and uncontrolled confounders,” they added.

Not recommended

The results of the current study also supported those of other trials that examined the clinical efficacy of oral ivermectin early treatment among mild COVID-19 patients. [JAMA 2021;325:1426-1435; Trials 2020;21:965; J Pharm Pharm Sci 2021;24:343-350]

“While these studies varied in population characteristics, number of subjects, medication protocol and the definition of outcomes, their main findings were universal,” the researchers said.

“Ivermectin early treatment was not clinically superior to the placebo for multiple outcomes among mild COVID-19 patients,” they added.

These data confirm the conclusions of the World Health Organization on the pooled data from 16 randomized controlled trials and the National Institutes of Health’s COVID-19 treatment guidelines, which do not recommend ivermectin as standard care for patients with mild COVID-19. [https://www.who.int/news-room/feature-stories/detail/who-advises-that-ivermectin-only-be-used-to-treat-covid-19-within-clinical-trials; https://emergency.cdc.gov/han/2021/han00449.asp]

The current study was limited by the lack of data on SARS-CoV-2 vaccination, which might be a potential confounder.

“Ivermectin is a known antiparasitic agent that has been investigated as an antiviral agent against COVID-19,” the researchers said.