Ivermectin disappoints in new trial of COVID-19 patients

The anthelmintic agent ivermectin, tested in the EPIC* trial of 476 patients, did not significantly shorten symptom duration in adults with mild COVID-19.

Ivermectin is widely seen as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. But in this double-blind randomized controlled trial, the duration of symptoms was not significantly different for patients treated with a 5-day course of ivermectin vs placebo (median time to resolution of symptoms, 10 vs 12 days; hazard ratio [HR] for resolution of symptoms, 1.07). [JAMA. 2021;325:1426-1435]

The most commonly reported adverse effects were headache in 104 patients (52 percent) in the ivermectin group and 111 (56 percent) in the placebo group. The most common serious adverse event was multi-organ failure, which occurred in four patients (two in each group).

Not for mild COVID-19

“The findings do not support the use of ivermectin for treatment of mild COVID-19,” said the researchers led by Dr Eduardo Lopez-Medina from the Centro de Estudios en Infectología Pediátrica in Cali, Colombia. “Larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.”

Interest in ivermectin has snowballed after the release of two publications in 2020: a preprint study that has since been taken down, and an in vitro study that never progressed to clinical trials. [Antiviral Res 2020 Jun;178:104787]

In a more recent study, early viral clearance of SARS-CoV-2 was observed in ivermectin-treated patients, indicating that early intervention with this agent may limit viral replication within the host. [Int J Infect Dis 2021;103:214-216]

However, “most of these studies had incomplete information and significant methodological limitations,” commented the US National Institutes of Health (NIH). In its COVID-19 Treatment Guidelines, the NIH said there is insufficient evidence to recommend either for or against the use of ivermectin for COVID-19.

A closer look at ivermectin

Lopez-Medina and colleagues sought to investigate ivermectin in patients with mild disease and symptoms for ≤7 days who were confined at home or hospitalized. The patients were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. They were randomly assigned in a 1:1 ratio to receive oral ivermectin 300 μg/kg of body weight (n=200) or placebo (n = 200) daily for 5 days. The primary outcome was time to resolution of symptoms within a 21-day follow-up period.

By day 21, 82 percent in the ivermectin group and 79 percent in the placebo group had their symptoms resolved.

Let’s hear from the WHO, FDA

In March, the World Health Organization has advised that evidence on the use of ivermectin to treat COVID-19 is “inconclusive,” and that until more data is available, the drug should not be used outside of clinical trials.

The US Food and Drug Administration (FDA) earlier warned the public against using ivermectin to treat or prevent COVID-19, citing multiple reports of patients being hospitalized or needing medical support after self-medicating with ivermectin.

The drug is approved to treat onchocerciasis  (also known as river blindness, which is caused by a type of worm that causes severe itching, skin bumps, and vision problems) and strongyloidiasis (infection with a type of roundworm that enters through the skin, moves through the airways, and lives in the intestines). Ivermectin is also used for lice infestation and scabies but is not FDA-approved for the treatment of viral infection.

Interactions with blood thinners are also potentially dangerous even at the levels specified in approved uses, the FDA added.

“You can also overdose on ivermectin,” the agency said. “Taking large doses of this drug is dangerous and can cause serious harm.” Some side effects included nausea, vomiting, diarrhoea, hypotension, allergic reactions, dizziness, ataxia, seizures, coma, and even death.

“Using any treatment for COVID-19 that is not approved or authorized by the FDA, unless part of a clinical trial, can cause serious harm,” the agency warned.

Currently, there are over 30 clinical trials testing ivermectin for COVID-19.