For decades, ivermectin has been widely used to treat parasitic infections. Early in the pandemic, when researchers were trying thousands of old drugs against Covid-19, laboratory experiments on cells suggested that ivermectin might block the coronavirus.
At the time, sceptics pointed out that the experiments worked thanks to high concentrations of the drug — far beyond safe levels for people. Nevertheless, 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.
Around the world, researchers carried out small clinical trials to see if the drug treated the disease. In December 2020, Andrew Hill, a virus expert at the University of Liverpool in England, reviewed the results of 23 trials and concluded that ivermectin appeared to significantly lower the risk of death from Covid-19.
If larger trials confirmed those findings, Hill said in a presentation at the time, "this really is going to be a transformative treatment."
Ivermectin's popularity continued to climb in the pandemic's second year. Podcaster Joe Rogan promoted it repeatedly on his shows. In a single week in August, US insurance companies spent US$2.4 million paying for ivermectin treatments
But not long after Hill published his review this past summer, reports surfaced that many of the studies he included in the analysis were flawed and, in at least one case, alleged to be fraudulent. Hill retracted his original study and started a new one, which he published in January.
On their second review, Hill and his colleagues focused on the studies least likely to be biased. In that stricter survey, ivermectin's benefit vanished.
Still, even the best studies on ivermectin and Covid-19 were small, with a few hundred volunteers at most. Small studies can be vulnerable to statistical flukes that suggest positive effects where none actually exist. But larger studies on ivermectin were underway at the time, and those promised to be more rigorous.
In Brazil, researchers set up a clinical trial known as Together in June 2020 to test Covid-19 patients with a number of widely used drugs, including ivermectin. The treatments were double-blinded, meaning that neither the patients nor their medical staff knew whether they received a Covid-19 treatment drug or a placebo.
In one round of the trial, the researchers found promising evidence that an antidepressant drug called fluvoxamine reduced the need for hospitalisation by one-third. The researchers published their results in October in The Lancet Global Health.
In a new study published Wednesday, the Together team reported on its ivermectin data. Between March and August 2021, the researchers provided the drug to 679 patients over the course of three days.
The results were clear: Taking ivermectin did not reduce a Covid-19 patient's risk of ending up in the hospital.
The researchers zeroed in on different groups of volunteers to see if they experienced benefits that others didn't. For example, it might be possible that ivermectin only worked if taken early in an infection. But volunteers who took ivermectin in the first three days after a positive coronavirus test turned out to have worse outcomes than did those in the placebo group.
Hill was impressed with the results. "They have run a high-quality, placebo-controlled trial," he said. He also expressed impatience with the New England Journal of Medicine for taking months to publish the results: "I don't understand the delay with this trial from NEJM."
Julia Morin, a spokesperson for the journal, declined to comment on the delay. "We don't comment on the editorial process, as it's confidential," she said in an email.
Hill has run his analysis of ivermectin studies again, this time including the new data from the Together trial. All told, his analysis included more than 5,000 people. And once more, he saw no benefit from ivermectin.
Still, there are several ongoing randomised trials of ivermectin, with thousands of volunteers, that have yet to share their results. The National Center for Advancing Translational Sciences, which is part of the NIH, has for more than a year been running one closely watched trial of ivermectin and several other drugs for Covid-19 patients. But it has yet to release results.
Sarah Dunsmore, a program director in the clinical innovations division at the centre, said that researchers were analysing the first batch of results on ivermectin and would release them in two to three months.
Boulware doubted that the additional trials would come to a different conclusion, since the Together trial was so large and carefully designed. "Rarely would you expect to find something different," he said.
Dr. Paul Sax, an infectious disease expert at Brigham and Women's Hospital in Boston who was not involved in the Together trial, shared Boulware's view.
"I welcome the results of the other clinical trials and will view them with an open mind, but at some point it will become a waste of resources to continue studying an unpromising approach," he said.
This article originally appeared in The New York Times.
Written by: Carl Zimmer
© 2022 THE NEW YORK TIMES
