Study: High Dose Ivermectin Not Effective for Outpatients With COVID-19


Results of the ACTIV-6 study showed that high dose ivermectin use did not demonstrate a clinical benefit for mild to moderate COVID-19.

Since the start of the COVID-19 pandemic, scientists and clinicians have looked to already available medications in hopes that they could be repurposed to treat the SARS-CoV-2 virus. Several of these agents have demonstrated activity in vitro, but then failed to provide clinically significant benefits in human studies.1 One of the most controversial medications has been ivermectin, an antiparasitic that is over 4 decades old and has been used in humans since 1986.2

Ivermectin (Stromectol; Merck) garnered interest by many due to its ease of use and inexpensive cost. Unfortunately, most of the early studies evaluating ivermectin for the treatment of COVID-19 had significant methodological flaws. Further, more recent and better designed studies have failed to demonstrate clinical benefit in mild to moderate COVID-19 cases at doses of 400 μg/kg once a day for 3 days. It was suggested that the studies did not detect a benefit because both the dose and the duration of therapy were suboptimal.

On February 20, results of a placebo-controlled study evaluating ivermectin 600 μg/kg once a day for 6 days in 1334 outpatients were published. The study was conducted as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) study, an ongoing national adaptive platform study designed to evaluate already FDA-approved medications for possible benefit in the management of COVID-19.2 The study took place from February to July 2022, meaning that at least some of the recent Omicron subvariants were likely infectious cause.

The 600 μg/kg dose was specifically chosen based on results modeling studies and a proof-of-concept clinical study that indicated this dose would result in plasma levels necessary for in vitro anti-SARS-CoV-2 activity.1 Overall, the study was well designed and over 83% of patients in both groups had received at least 2 doses of the COVID-19 vaccine.

The results of the ACTIV-6 study showed that high dose ivermectin use did not demonstrate a clinical benefit for mild to moderate COVID-19.1 The median time to recovery (defined as time from receipt of medication to achieving the third of 3 days of recovery) was 11 days in both the ivermectin and placebo groups. The drug also failed to reduce 28-day mortality, hospitalizations, emergency department or urgent care visits, or time unwell.

However, it is worth noting that only 5 hospitalizations or deaths occurred in the trial, but this includes 1 death due to a non-COVID-19 cause. The authors conducted analysis to determine if any variables may have impacted the results and found no significant difference among any of the subgroups evaluated. While the drug did not seem to benefit patients with mild to moderate COVID-19, it did not seem to cause much harm either. Further, adverse event rates were similar to placebo (9.2% vs. 7.1%).

The study reinforces previous evidence that ivermectin lacks clinical activity against SARS-CoV-2. The study’s design, choice of medication regimen, and analysis address many concerns brought up with previous trials. The study is also a good reminder of the importance of human studies; while the early days of the pandemic may have necessitated a less structured approach to research, the current availability of vaccines and effective antivirals that did not exist in 2020 permit the evaluation of COVID-19 medication, novel or repurposed, through clinical studies at the standard expectation. At this time, it does not appear that ivermectin offers anything more than a placebo effect for outpatients with COVID-19.


  1. Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19. JAMA. 2023. doi:10.1001/jama.2023.1650
  2. ACTIV-6 Study. Welcome to the ACTIV‑6 study. ACTIV-6 Study website. Accessed February 22, 2023.
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