WASHINGTON — There were no differences in relief from mild-to-moderate COVID-19 symptoms for patients on ivermectin versus placebo, according to the ongoing ACTIV-6 trial.
Among >1,000 vaccinated and unvaccinated patients, the median time to recovery was 12 days for those in the ivermectin group and 13 days in the placebo group, reported Matthew McCarthy, MD, of Weill Cornell Medicine in New York City, at IDWeek.
As a result, the hazard ratio for improvement in time to recovery was 1.07 (95% credible interval 0.96-1.17, posterior P=0.91), McCarthy and colleagues stated in JAMA, where the results were simultaneously published.
He noted that the current trial was conducted during Delta and Omicron variant surges in the country (June 23, 2021 through Feb. 4, 2022).
McCarthy said during the presentation that treatment with two other repurposed agents — the antidepressant fluvoxamine (Luvox) and the inhaled steroid fluticasone — did not offer significantly better outcomes than placebo. “We observed no significant differences in relief of mild-to-moderate symptoms between participants taking ivermectin, fluticasone, or fluvoxamine and participants taking placebo. There was no difference observed in the number of hospitalizations or deaths between patients taking ivermectin, fluticasone, or fluvoxamine and participants taking placebo. There were no safety concerns identified in any arm,” he stated.
“These results are consistent with what we have seen in other trials with these agents,” said IDWeek session co-moderator Adarsh Bhimraj, MD, of Houston Methodist.
“This is a huge platform trial,” he told MedPage Today. “It’s strength is in the numbers of patients included, and that it was conducted later in the pandemic which is more relevant to us now, and it is also concordant with other studies.”
Bhimraj stated that “there were no surprises with these results of ACTIV-6, which…is good,” adding that studies showing which treatments do not work have as much value as those that demonstrate which treatments do work.
He also pointed out that “across all these trials with these different agents, the safety signals are not that bad.”
McCarthy’s group reported that there were 10 hospitalizations or deaths in the ivermectin group and nine in the placebo group (1.2% vs 1.2%, HR 1.1, 95% CrI 0.4-2.6). The most common serious adverse events were COVID-19 pneumonia with five cases in the ivermectin group and seven in the placebo group, along with venous thromboembolism (one and five cases, respectively). There was one death in the ivermectin group.
For the ivermectin arm of ACTIV-6, 814 people were on ivermectin (400 μ6/kg) and 774 people were on placebo, daily for 3 days. Less than half reported receiving at least two doses of a SARS-CoV-2 vaccine. Median patient age was 48, 57% were women, and about 80% were white. There were 656 patients in the fluticasone arm and 621 on placebo. About a third of the patients had not had any COVID vaccine. Median age was about 46, 63% were women, and about 80% were white. Finally, there were 674 patients on fluvoxamine and 624 patients on placebo. About two-thirds had received at least two doses of the vaccine. They had a median age of 48 years, 58% were women, and about 80% were white.
McCarthy and colleagues acknowledged that “the inclusion criteria allow[s] for a broad study population, this study failed to achieve the level of representation desired for underrepresented populations in terms of racial and ethnic diversity,” which was a study limitation.
Still, they concluded that the “findings do not support the use of ivermectin in patients with mild to moderate COVID-19…this study adds to the growing evidence that there is not a clinically relevant treatment effect of ivermectin at this dose and duration.”
ACTIV-6 is funded by the National Center for Advancing Translational Sciences (NCATS), and supported by the Vanderbilt University Medical Center Recruitment Innovation Core, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, Vanderbilt University Medical Center Clinical and Translational Science Award/NCATS, and REDCap infrastructure.
McCarthy disclosed no relationships with industry. Co-authors disclosed relationships with, and/or support from, multiple entities including NCATS.