High-dose ivermectin does not reduce COVID-19 symptom duration among mild-to-moderate outpatients

By Pooja Toshniwal PahariaFeb 27 2023Reviewed by Benedette Cuffari, M.Sc.

In a recent study published in JAMA, researchers evaluate the efficacy of ivermectin in a maximum dosage of 600 μg/kg/day over six days in treating early mild-to-moderate coronavirus disease 2019 (COVID-19).

Study: Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19 A Randomized Clinical Trial. Image Credit: Sonis Photography / Shutterstock.com

Background

The continual emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with greater transmissibility and immune evasiveness has threatened the efficacy of COVID-19 vaccines and therapeutic agents such as antiviral drugs and monoclonal antibodies. As a result, research is needed to identify new drugs with anti-SARS-CoV-2 activity.

It remains unknown whether a daily dose of ivermectin 600 μg/kg can reduce the duration of symptoms or prevent hospital admissions in individuals with mild-to-moderate SARS-CoV-2 infections in outpatient settings.

About the study

In the present accelerating COVID-19 therapeutic interventions and vaccines 6 (ACTIV-6) randomized controlled trial, researchers investigate whether 600 μg/kg/day of ivermectin for six days reduces the duration of symptoms among individuals with symptomatic mild-to-moderate SARS-CoV-2 infection in outpatient settings.

In the ongoing, national, double-blinded, randomized, decentralized, and placebo-controlled clinical trial investigating repurposed drugs for treating individuals with mild or moderate SARS-CoV-2 infections 1,206 confirmed-SARS-CoV-2-positive individuals 30 years or older who experienced at least two acute symptoms for less than one week were recruited across 93 sites throughout the U.S.

Individuals were recruited between February 16, 2022, and July 22, 2022, and followed up through November 10, 2022. COVID-19 diagnosis was confirmed by polymerase chain reaction (PCR) assay or SARS-CoV-2 antigen testing, including at-home tests.

In the analysis, 602 participants received ivermectin at a maximum dosage of 600 μg/kg/day, whereas 604 individuals received a placebo daily for six days. The prime study outcome was the duration of sustained COVID-19 recovery or at least three successive and asymptomatic days.

Secondary study outcomes included hospital admissions, deaths, or emergency department visits by COVID-19 outpatients through week four. The team excluded individuals who were hospitalized, consumed ivermectin within the two previous weeks, or had known contraindications or allergies to ivermectin.

The other study drug under investigation during the period was fluvoxamine. Proportional hazards regression modelling was performed and the hazard ratios (HR) were calculated. Ivermectin was supplied in bottles comprising 7.0 mg tablets to participants’ homes.

Dosing schedules were based on participants’ weight. Participants were asked to complete daily assessments and report adverse events through week two.

Self-documented data were obtained on individual demographics including age, sex, body mass index (BMI), race, ethnicity, history of medical diseases, concomitant medications, COVID-19 symptoms, the status of vaccination, and responses to questionnaires distributed for assessing the quality of life.

Study findings

Among the study participants, 59% were female with a median age of 48 years and 84% were fully vaccinated against COVID-19. In both groups, the median duration for sustained recovery from COVID-19 was 11 days.

The median dose of ivermectin was 498 μg/kg/day. In the large vaccinated outpatient population, the posterior probability for benefit using ivermectin was 0.7 for the primary outcome of time to COVID-19 recovery. The posterior probability of reduction of COVID-19 symptom duration by one or more days using ivermectin was less than 0.10% with an HR value of 1.0.  

Among ivermectin-treated individuals, 6% were admitted to hospitals, died, or visited the emergency department as compared to 36 placebo-treated individuals with an HR 1.0.  Among ivermectin-treated individuals, four were hospitalized and one died. The number of corresponding individuals was two and zero among placebo-treated individuals.

The team did not commonly observe adverse events in any group. Adverse events documented more than two times following ivermectin treatment included cognitive impairments, blurring of vision, increased sensitivity to light, dizziness, asthma, and photophobia. The death of an ivermectin-treated individual was documented as occurring by accident and was not associated with COVID-19 or ivermectin use.

The difference in the duration spent feeling sick due to COVID-19 was estimated as three hours and 20 minutes faster with ivermectin as compared to the placebo. The COVID-19 clinical progression scale scores at weeks one, two, and four could not meet predetermined threshold values for therapeutic benefit from ivermectin.

Conclusions

Overall, the study findings showed that ivermectin at a maximum dose of 600/μg/kg/day treatment for six days did not reduce the duration of sustained COVID-19 recovery among mild-to-moderate outpatients with SARS-CoV-2 Omicron variant infections. Taken together, these data do not support the use of in treating individuals with mild-to-moderate SARS-CoV-2 infections.