Among ambulatory patients with mild-to-moderate COVID-19, doses of ivermectin of up to 600 mg/day for 6 days failed to improve time to sustained recovery, researchers report. “No evidence of benefit was observed for secondary clinical outcomes, including the composite of hospitalization, death, or acute care visits,” the authors write. “Hospitalization and death were uncommon in this largely vaccinated population. These findings do not support the use of ivermectin in outpatients with COVID-19.”
The Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform is conducting randomized clinical trials to evaluate repurposed therapies among outpatients with mild-to-moderate COVID-19. In this part of the research, 1,206 participants older than 30 years with confirmed COVID-19 and at least 2 symptoms of acute infection for 7 days or less were randomized to ivermectin up to a maximum targeted dose of 600 μg/kg daily or placebo for 6 days. The trial used a primary outcome of time to sustained recovery (at least 3 consecutive days without symptoms) and 7 secondary outcomes (a composite of hospitalization, death, or urgent/emergent care utilization by day 28).
“The median (IQR) age of participants was 48 (38-58) years, 713 (59.1%) were women, and 1,008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses,” write the authors. “The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups.”
Editor’s Note: “At the doses and durations tested in these studies, ivermectin does not appear to be associated with serious adverse effects,” JAMA editors write. “However, a generally well-tolerated therapy that lacks efficacy can still be dangerous, particularly if it results in patients forgoing other interventions with proven efficacy, such as evidence-based COVID-19 treatments or vaccination against SARS-CoV-2. Ivermectin has been used throughout the pandemic. Although the current prevalence of ivermectin use in the US and globally is difficult to determine, reports in the lay media as well as our own experience as clinicians suggest that use of ivermectin for COVID-19 has not fully abated, fueled in part by real or perceived lack of access to effective therapies, continued confusion or misinformation, and active disinformation about ivermectin’s efficacy, including by physicians.”
Editorial: Assessing the ethics of clinical research and the need to manage “persistent uncertainty,” editorialists write: “These findings are consistent with previous research, including 3 other randomized trials of different doses and duration of ivermectin. However, there are currently more than 10 trials of ivermectin recruiting participants on ClinicalTrials.gov. After considering factors that can influence the persistence of clinical equipoise, we argue that decisions about what investigations to undertake must be responsive to the relative social value of continuing to reduce uncertainty around one intervention, and stakeholders must consider whether scarce time, resources, and participant effort could be better invested examining other questions.”