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COVID-19 patients treated in a randomized trial with the anti-parasitic drug ivermectin did no better than a placebo group, Colombian researchers said.

Median time to recovery among mild COVID-19 patients in the ivermectin group was 10 days versus 12 days among those receiving placebo, and rates of symptom resolution at day 21 were about equal, reported Eduardo López-Medina, MD, of Centro de Estudios en Infectología Pediátrica, and colleagues, writing in

But the trial was far from perfect. The initial primary outcome was time from randomization until worsening of symptoms by two points on an ordinal scale, but few patients reached this endpoint in the expected time, meaning the sample size needed to maintain sufficient power was "unattainable." Therefore, the primary endpoint was changed to time from randomization to symptom resolution by day 21, and the original sample size was retained.

As well, a labeling error occurred during the trial, where ivermectin was given to all patients from Sept. 29 to Oct. 15, so the protocol was amended, and these patients were excluded from the primary analysis. Additional patients were then recruited to retain the originally calculated study power.

Despite these problems, López-Medina and colleagues said the findings remained valid within the confines of its other limitations. These included lack of power for other endpoints of interest, such as illness progression, given its final enrollment of 398 patients.

Ivermectin has garnered considerable buzz as a drug to treat COVID-19, with several countries including it in their guidelines, but the authors pointed to a lack of research on the effects of ivermectin on COVID-19 in the clinical setting.

Moreover, the NIH COVID-19 guidelines cited to either recommend for or against use of ivermectin, and called for more research and clinical trials on the subject.

"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," López-Medina and co-authors wrote.

The was a randomized, double-blind, single-center study conducted from July 15 to Dec. 21, 2020. Patients were eligible if they were non-pregnant or breastfeeding adults with mild disease, defined as a positive RT-PCR or antigen test for SARS-CoV-2, and if they were at home or hospitalized, but not receiving high-flow mechanical ventilation.

Patients were assigned 1:1 to receive 300 μg/kg of body weight per day of ivermectin or placebo, for 5 days orally. They were instructed to take it on an empty stomach, except the first day, when it was administered following screening and randomization. Patients were then followed up on days 2, 5, 8, 11, 15, and 21.

Primary outcome was complete resolution of symptoms within the 21-day period, using an eight-category ordinal scale, ranging from 0 (no clinical evidence of infection) to 7 (death). Time to recovery was counted as the first day during the 21-day period when patients reported a score of 0.

Overall, 476 patients were randomized, including those excluded on account of the dosing error (they remained in the as-treated population).

Patient median age was 37, and 58% were women. Almost 80% had no comorbidities at baseline. Over three-quarters of patients reported myalgia and headache, and 56% reported loss of smell.

There was no significant difference in time to resolution of symptoms between groups (HR 1.07, 95% CI 0.87-1.32, P=0.53). In addition, symptoms resolved in 82% of the ivermectin group and 79% of the placebo group by 21 days.

Few patients in either group experienced clinical deterioration of more than two points on the ordinal scale (2% in ivermectin vs 3.5% in placebo), and odds of improving score in the ordinal scale were not significantly different between groups either. There was also no significant difference in the proportion of patients requiring escalation of care in both groups (2% vs 5%, respectively).

Adverse events were reported in the majority of both groups (77% vs 81.3%) between randomization and day 21, leading to discontinuation in 15 patients in the ivermectin group and five in the placebo. There were four serious adverse events (two apiece in each group), but none were judged to be related to the study medication.

Limitations to the study, the researchers said, included that it was not conducted or completed according to the original design; that it may have been underpowered to detect a smaller, clinically meaningful reduction in the primary endpoint; and virological assessments were not included, only clinical characteristics.

The authors concluded that larger trials would be needed "to understand the effects of ivermectin on other clinically relevant outcomes."

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