The antiparasitic drug ivermectin, which has gained popularity as an alternative treatment for Covid-19 despite a lack of strong research to back it up, has shown no sign of relieving the disease, according to the results of a large clinical trial published Wednesday.
The study, which compared more than 1,300 people infected with the coronavirus in Brazil who received either ivermectin or a placebo, effectively ruled out the drug as a treatment for Covid, the study authors said.
“There’s really no evidence of benefit,” said Dr. David Boulware, an infectious disease expert at the University of Minnesota.
The researchers shared a summary of those findings in August during an online presentation hosted by the National Institutes of Health, but the full data set had not yet been published in the New England Journal of Medicine.
“Now that people can dive into the details and data, hopefully this will steer the majority of physicians away from ivermectin to other therapies,” said Dr. bowlware.
For decades, ivermectin has been widely used to treat parasitic infections. At the beginning of the pandemic, as researchers tried thousands of old drugs against Covid-19, laboratory experiments on cells suggested that ivermectin could block the coronavirus.
At the time, skeptics pointed out that the experiments worked thanks to high concentrations of the drug — well above safe levels for humans. Despite this, some doctors began prescribing ivermectin for Covid-19, despite a warning from the Food and Drug Administration that it was not approved for such use.
Researchers around the world were conducting small clinical trials to see if the drug would treat the disease. In December 2020, Andrew Hill, a virologist at the University of Liverpool in England, reviewed the results of 23 studies and concluded that ivermectin appeared to significantly reduce the risk of death from Covid-19.
If larger studies confirmed these results, Dr. Hill in a presentation at the time, “this is really going to be a transformative treatment.”
Ivermectin’s popularity continued to soar in the second year of the pandemic. Podcaster Joe Rogan repeatedly promoted it on his shows. In a single week in August US insurance companies consumed $2.4 million for ivermectin treatments
But not long after Dr. Hill published his report last summer, reports surfaced that many of the studies he included in the analysis were flawed, and in at least one case suspected of being fraudulent. dr Hill withdrew his original study and began a new one, which he published in January.
In their second review, Drs. Hill and his colleagues point to the studies least likely to be biased. In this more rigorous survey, the benefits of ivermectin disappeared.
Still, even the best studies on ivermectin and Covid have been small, with a few hundred volunteers at most. Small studies can be prone to statistical hits that suggest positive effects where none exist. However, larger studies of ivermectin were underway at the time, and these promised to be more rigorous.
In Brazil, researchers set up a clinical trial called TOGETHER in June 2020 to test Covid patients with a range of widely used drugs, including ivermectin. The treatments were double-blind, meaning neither the patients nor their medical staff knew whether they were receiving a Covid treatment drug or a placebo.
In one round of the study, researchers found promising evidence that an antidepressant called fluvoxamine reduced the need for hospitalization by a third. The researchers published their findings in The Lancet Global Health in October.
In a new study published Wednesday, the TOGETHER team reports on their ivermectin data. Between March and August 2021, the researchers administered the drug to 679 patients over three days.
The results were clear: Taking ivermectin did not reduce a Covid patient’s risk of ending up in the hospital.
Researchers focused on different groups of volunteers to see if they experienced benefits that others did not. For example, it might be possible that ivermectin only works if taken early in an infection. But volunteers who took ivermectin for the first three days after testing positive for coronavirus had worse results than those in the placebo group.
dr Hill was impressed with the results. “They did a high-quality, placebo-controlled study,” he said. He also expressed his impatience to the New England Journal of Medicine that it had taken months to publish the results: “I don’t understand the delay in this study from NEJM.”
Julia Morins, a spokeswoman for the magazine, declined to comment on the delay. “We do not comment on the editorial process as it is confidential,” she said in an email.
dr Hill re-ran his analysis of ivermectin studies, this time including the new data from the TOGETHER study. Overall, his analysis included more than 5,000 people. And once again, he saw no benefit from ivermectin.
Still, there are several ongoing randomized trials of ivermectin involving thousands of volunteers who are yet to share their results. The National Center for Advancing Translational Sciences, part of the NIH, has been conducting a closely monitored study of ivermectin and several other drugs for Covid patients for more than a year. But it has yet to release results.
dr Sarah Dunsmore, program director in the clinical innovation division at NCATS, said the researchers were analyzing the first set of results on ivermectin and would be publishing them in two to three months.
dr Boulware doubted that the additional studies would come to a different conclusion because the TOGETHER study was so large and carefully designed. “One would seldom expect to find anything else,” he said.
dr Paul Sax, an infectious disease expert at Brigham and Women’s Hospital in Boston who was not involved in the TOGETHER study, shared Dr. bowlware.
“I welcome the results of the other clinical trials and will look at them with an open mind, but at some point it becomes a waste of resources to continue investigating a futile approach,” he said.