The antiparasitic drug ivermectin, which has gained popularity as an alternative treatment for Covid-19 despite a lack of strong research to support it, showed no signs of improving the disease, according to results of a large trial. clinical published Wednesday.

The study, which compared more than 1,300 people infected with the coronavirus in Brazil who received ivermectin or a placebo, effectively ruled out the drug as a treatment for Covid, the study authors said.

“There’s really no sign of benefit,” said Dr. David Boulware, an infectious disease expert at the University of Minnesota.

The researchers shared a summary of these findings in August at an online conference presentation hosted by the National Institutes of Health, but the full dataset had not been published in the New England Journal of Medicine until now.

“Now that people can delve into the details and the data, hopefully this will steer the majority of doctors away from ivermectin to other therapies,” Dr. Boulware said.

For decades, ivermectin has been widely used to treat parasitic infections. Early in the pandemic, when researchers were trying thousands of old Covid-19 drugs, lab experiments on cells suggested that ivermectin might block the coronavirus.

At the time, skeptics pointed out that the experiments worked with high concentrations of the drug, far beyond safe levels for people. Nevertheless, some doctors have started prescribing ivermectin for Covid-19, despite a Warning from the Food and Drug Administration that it has not been approved for such use.

Around the world, researchers conducted small clinical trials to see if the drug treated the condition. In December 2020, Andrew Hill, a virologist at the University of Liverpool in England, reviewed the results of 23 trials and concluded that ivermectin appeared to significantly reduce the risk of death from Covid-19.

If larger trials confirm these results, Dr Hill noted in a presentation at the time, “this is truly going to be a transformative treatment.”

Ivermectin’s popularity continued to climb in the second year of the pandemic. Podcaster Joe Rogan promoted him several times on his shows. In a single week in August, U.S. insurance companies spent $2.4 million to pay for ivermectin treatments

But soon after Dr. Hill published his review last summer, reports surfaced that many of the studies he included in the analysis were flawed and, in at least one case, allegedly fraudulent. Dr. Hill went back to his initial study and started a new one, which he published in January.

In their second review, Dr. Hill and his colleagues focused on the studies least likely to be biased. In this stricter investigation, the benefits of ivermectin disappeared.

Yet even the best studies on ivermectin and Covid were small, with a few hundred volunteers at most. Small studies can be vulnerable to statistical vagaries that suggest positive effects where none actually exist. But larger studies of ivermectin were underway at the time, and these promised to be more rigorous.

In Brazil, researchers set up a clinical trial known as TOGETHER in June 2020 to test Covid patients with a number 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 a series of trials, researchers found promising evidence that an antidepressant called fluvoxamine reduced the need for hospitalization by a third. The researchers published their findings in October in The Lancet Global Health.

In a new study published on Wednesday, the TOGETHER team reported their data on ivermectin. Between March and August 2021, researchers provided the drug to 679 patients for three days.

The results were clear: taking ivermectin did not reduce a Covid patient’s risk of ending up in hospital.

The researchers focused on different groups of volunteers to see if they received benefits that others did not. For example, ivermectin may only work if taken at the start of an infection. But volunteers who took ivermectin within the first three days after the onset of Covid symptoms were found to perform worse than those in the placebo group.

Dr. Hill was impressed with the results. “They conducted a high-quality placebo-controlled trial,” he said. He also expressed his impatience with the New England Journal of Medicine for taking months to publish the results: “I don’t understand the delay in this NEJM trial.

Julia Morin, a spokeswoman for the newspaper, 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 again ran his analysis of the ivermectin studies, this time including new data from the TOGETHER trial. In total, his analysis included more than 5,000 people. And again, he saw no benefit from ivermectin.

Still, there are several ongoing randomized trials of ivermectin, with thousands of volunteers, who have yet to share their results. The National Center for Advancing Translational Sciences, part of the NIH, has been running a closely watched program for more than a year. ivermectin trial and several other drugs for Covid patients. But it has not yet published any results.

Dr. Sarah Dunsmore, program director in the clinical innovations division of NCATS, said the researchers were analyzing the first batch of ivermectin results and would publish them in two to three months.

Dr. Boulware doubted that the additional trials would lead to a different conclusion because the TOGETHER trial was so large and carefully designed. “You rarely expect to find anything 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 Dr. Boulware’s view.

“I welcome the results of other clinical trials and will look at them with an open mind, but at some point it will become a waste of resources to continue studying an unpromising approach,” he said.