Evidence Still Lacking to Support Ivermectin as Treatment for COVID-19


SciCheck Digest

Randomized controlled trials haven’t found ivermectin is beneficial in treating COVID-19, although results for ongoing studies will provide a more definitive answer. Yet, a video presents two weak studies as “powerful” and “overwhelming” evidence that the medication works to combat COVID-19. 

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After more than 80 studies have evaluated the use of ivermectin, an antiparasitic medication, to treat or prevent COVID-19 in humans, the National Institutes of Health, the Centers for Disease Control and Prevention and the World Health Organization have determined there is insufficient evidence to recommend using ivermectin to treat COVID-19. As we’ve reported, large clinical trials to determine its safety and effectiveness are ongoing, and results are expected in about a month. 

But so far, randomized controlled trials have shown no evidence of a clinical benefit for ivermectin. And the medication has not been approved or authorized by the Food and Drug Administration to prevent or treat COVID-19. 

Yet, some people keep touting the effectiveness of the medication against COVID-19. In February, we fact-checked a misleading claim about ivermectin and the NIH, as well as false claims that a Japanese company had found ivermectin had worked in a phase 3 clinical trial, which was based on an inaccurate news article. On March 6, John Campbell, who has a doctorate in nursing education but is not a physician, posted a video about the drug that amassed nearly a million views. It incorrectly presented two weak studies as “powerful” and “overwhelming” evidence that the drug works to combat the disease. 

“Why isn’t this in the newspapers?” Campbell asks his viewers after reviewing preliminary results of a study that was later canceled by its authors and the results of a flawed study. “This is why I think ivermectin is going to be one of the big scandals of this [pandemic]. It’s almost as if information has been deliberately suppressed throughout the pandemic, to be quite honest.”

On March 14, Campbell replaced the original video with a new version that eliminates the discussion of the first study.

Information on the ongoing and completed studies on ivermectin has been widely available, and the public can access the information on the NIH website. The studies Campbell highlights are not in the news because both have significant limitations and are not randomized controlled trials, which are considered the gold standard of clinical research. Such trials randomly assign participants to treatment or control groups, enabling researchers to more confidently evaluate whether a treatment led to different results.

Photo illustration by Rafael Henrique/SOPA Images/LightRocket via Getty Images.

We reached out to Campbell to ask why he didn’t include important context about the two studies — and why he omitted mention of stronger evidence from randomized controlled trials that have not found ivermectin to be helpful with COVID-19. But we did not hear back from him.

In his latest video, Campbell said he deleted his March 6 video from his YouTube channel because one of the two studies featured in that video was “flawed.” The new video, however, still shows original footage from the March 6 video of Campbell discussing the second study, which as we’ll explain later, has significant problems. Campbell’s original video still remains in other forms on Facebook and YouTube.

One of the latest results from a randomized clinical trial published in JAMA Internal Medicine on Feb. 18 came from Malaysia. The study found that treatment with ivermectin during the early stages of COVID-19 in 490 patients did not reduce the risk of progression to severe disease — 21.6% of the patients in the ivermectin group and 17.3% in the control group progressed to severe disease. 

Dr. Steven Chee Loon Lim, co-author of the study and an infectious disease physician at the Raja Permaisuri Bainun Hospital in Malaysia, told us in an email there were no “statistically significant effects in the rate of mechanical ventilation, ICU admission and mortality,” either.  

“Essentially, our study findings have dismissed the notion of ivermectin being a ‘miracle drug’ against COVID-19. Individuals infected with COVID-19 should not resort to self-medication with ivermectin. Having a false sense of recovery while taking an ineffective drug could lead to delay in seeking appropriate medical care, thus resulting in poorer outcomes,” Lim wrote.

Results of other ongoing clinical trials with over 1,000 participants each are expected soon. Dr. David Boulware, a professor of medicine at the University of Minnesota Medical School and an adviser for two large trials in the U.S., told us in an email that multiple trials “may likely publicly report results in April.” Both the Together trial in Brazil and the University of Minnesota Covid-Out trial in the U.S. are fully completed, he said. The ACTIV-6 trial, funded by the NIH, has completed follow-up of its ivermectin arm, and data are being analyzed. And the PRINCIPLE trial in the United Kingdom and another one in Japan are still recruiting, he said. 

Preliminary Study Showed Association, Not Causality

In his March 6 video, Campbell starts by reviewing an abstract presented at a virtual conference in November 2021 by researchers from the University of Miami. 

The authors retrospectively identified adults in the U.S. with a COVID-19 infection between Jan. 1, 2020, and July 11, 2021, using a large database of electronic health record information from a network of health care organizations. They then compared patients who had been treated with ivermectin (1,072 patients) with those who had been treated with remdesivir (40,536 patients), an FDA-approved antiviral treatment for hospitalized or high-risk non-hospitalized COVID-19 patients. They concluded ivermectin was associated with reduced mortality compared with remdesivir, with an odds ratio of 0.308. 

“In other words, you’re about 70% less likely to die if you take ivermectin compared to taking remdesivir,” says Campbell. “It’s pretty convincing data from national databases.”

Others also have used the abstract on social media to argue that it means ivermectin is effective against COVID-19. But the authors of the study have said that’s not how the data should be interpreted. 

Dr. Jose Gonzales Zamora, a co-author of the study and associate program director of the infectious disease fellowship at the University of Miami, told us the preliminary results of the observational study only show a statistical association between reduced mortality and ivermectin treatment, not causality. In other words, ivermectin isn’t necessarily the reason why that group of patients fared better.

“We can’t necessarily say, based on this kind of study, retrospective, that it was ivermectin what really reduced mortality because there are other confounding variables that could also affect that outcome,” Zamora said in a phone interview conducted in Spanish. “It is not correct to say ivermectin reduces mortality by 70%.” 

One of those confounding factors could be the age of the patients, he said, since the patients who received ivermectin were on average 10 years younger than those who were treated with remdesivir. (Even though the study tried to control for age and other factors using statistics, such adjustments in observational studies are imperfect and still at risk for bias.)

Another limitation of the study, Zamora said, was that the authors didn’t know how ill patients were when they received treatment. Since remdesivir is approved for hospitalized and high-risk patients, he explained, it’s possible those patients were sicker than the patients who received ivermectin.

The study is not proof of efficacy, Zamora said. And he clarified that the study shouldn’t be read as support for using ivermectin. Neither his research team nor his hospital had ever recommended the drug. One of the abstract’s most important conclusions — and one that Campbell omitted — Zamora pointed out, is that “further double-blinded placebo-controlled RCTs with large samples are required” to come to a definitive conclusion. Double-blinded randomized controlled trials are those in which neither the patients nor the researchers know which patients have been given the treatment versus the placebo while data is being collected.

The study was never peer-reviewed and was halted. “We did not submit the manuscript for a reason, weak evidence,” said its lead author, Iakov Efimenko, on Twitter. Zamora added that continuing the study made no sense once the results of randomized clinical trials failed to find any clinical benefit of using ivermectin for COVID-19 patients. 

Insufficient Evidence from Flawed Study

The second study Campbell presents in his video is a prospective, observational study done in the Brazilian city of Itajaí. Its authors include Dr. Pierre Kory, one of the strongest advocates of ivermectin in the U.S., and researchers in Brazil, Canada and Colombia — some of them also part of Kory’s pro-ivermectin nonprofit, called the Front Line COVID-19 Critical Care Alliance. The study concludes that the use of ivermectin reduced infections by half and reduced COVID-19 mortality and hospitalizations by 70% and 67%, respectively.  

“70% reduction in mortality in this study. I mean, this is just huge. And this is with a tiny dose of ivermectin every fortnight acting as a prophylactic, you know, why are people not talking about this?” Campbell says in his video. “The evidence just seems so powerful, present and overwhelming. I mean, 70%, how do you argue with a number like that?”

But the study is not a randomized, double-blind, placebo-controlled clinical trial, and it has multiple limitations. Health Feedback fact-checked stories published by the Gateway Pundit, Zero Hedge and the Blaze about an earlier draft of the study that was posted as a preprint in December.

“The study contained multiple methodological flaws that call the reliability of its conclusions into question. For example, there are indications that many people assigned to the ivermectin treatment group didn’t take the drug consistently, or stopped taking it after a while. It is therefore unclear whether any observed effect in this group can be reliably attributed to ivermectin treatment,” Health Feedback concluded. 

In a Twitter thread on Dec. 15, epidemiologist Gideon Meyerowitz-Katz detailed some of the study’s problems, including conflicts of interest and lack of controls for important confounders, such as variables that could increase the risk of getting COVID-19.

The study was then peer-reviewed and published on Jan. 15 in Cureus, an open access online medical journal that allows researchers to publish studies for free and faster than the traditional peer-reviewed journals — 11 days in this case. But some of the problems remain, as PolitiFact.com explained.

The study analyzed data of a citywide COVID-19 prevention program using ivermectin in Itajaí, Brazil, from July to December 2020, when vaccines were not available. The whole population of the city was offered ivermectin, to be taken for two consecutive days every 15 days. Out of 159,561 residents, 113,845 used ivermectin and 45,716 did not. But according to a statement released by the city of Itajaí in January 2021, the numbers of voluntary users fell with time — 138,216 took the first dose; two weeks later 93,970 took the second and third doses, and only 8,312 took the fourth and fifth. “That is, there was no biweekly continuity of the use of ivermectin, as recommended,” the statement said. 

A list of the authorized studies in Brazil using ivermectin as treatment for COVID-19 — provided to the Brazilian fact-checking coalition Comprova by the Brazilian National Research Ethics Commission — said the study “was registered with a sample of 9,956 participants.”

As we said, results of multiple large clinical trials on the safety and efficacy of the use of ivermectin to treat COVID-19 will be available in the coming months. They will provide a more definitive answer as to whether ivermectin is beneficial, or not, in treating COVID-19 patients. But for now, studies haven’t found the drug to be beneficial, and health officials have warned people not to self-medicate. 

Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.


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