A major clinical trial showed the malaria drug hydroxychloroquine had no benefit for patients hospitalized with Covid-19, likely closing the door to the use of the highly publicized medicine in the sickest patients — a use for which it was widely prescribed as the pandemic hit the U.S.
The results come from a study called RECOVERY, funded by the U.K. government, that sought to randomly assign large numbers of patients to multiple potential treatments in the country’s National Health Service. The goal was to rapidly get answers as to what worked and what didn’t.
“Today’s preliminary results from the RECOVERY trial are quite clear – hydroxychloroquine does not reduce the risk of death among hospitalized patients with this new disease,” University of Oxford epidemiologist Martin Landray, one of the study’s leaders, said in a statement. “This result should change medical practice worldwide and demonstrates the importance of large, randomized trials to inform decisions about both the efficacy and the safety of treatments.”
A total of 1,542 received hydroxychloroquine, and 3,132 received usual care. After 28 days of treatment, 25.7% of those on hydroxychloroquine and 23.5% of those received usual care had died, meaning those on hydroxychloroquine were 11% more likely to die. That difference was not statistically significant.
There was “no beneficial effect” on how long patients stayed in the hospital, or on other outcomes.
The results were shared via a press release, which the study’s lead authors shared on Twitter. They have not been peer-reviewed or published in a medical journal. The researchers said that full results would be shared as soon as possible.
Still, experts said even the top-line results showed they were meaningful.
“This is a hugely important finding that will likely end use of the drug in hospitalized Covid patients, given the other existing data as well,” said Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. Gellad said that he is curious to see the results of other ongoing studies, and that it is still an open question whether the medicine might work earlier in the disease. “We need real answers there as well,” he said.
Robert Califf, the former Food and Drug Administration commissioner and Alphabet employee, tweeted that the study “essentially rules out benefit of [hydroxychloroquine] in critically ill hospitalized patients.” He wrote that the results showed “no benefit; no major risk.”
In addition to being used for malaria, hydroxychloroquine is prescribed to treat conditions including rheumatoid arthritis and lupus. But it was known to increase the risk of arrhythmias.
The FDA still authorized emergency use of the drug in hospitalized patients in March, citing the possible safety issues.
Concerns were heightened by a May 22 study in British medical journal the Lancet. That study, which claimed to use a database from hundreds of hospitals around the world, seemed to indicate that treatment with hydroxychloroquine increased the death rate and the rate of arrhythmias.
But on Thursday, the Lancet retracted that study at the request of the authors after widespread questions about the database the study used and the company, Surgisphere, that had provided it. The authors not associated with Surgisphere had asked for the data to be audited, and Surgisphere refused. As such, they wrote, “we can no longer vouch for the veracity of the primary data sources.”
On Wednesday, another group of researchers released results from another randomized study, testing whether giving people hydroxychloroquine shortly after they have been exposed to someone with Covid-19 could prevent disease transmission. That study also showed no benefit, thought some researchers, including Gellad and Califf, say some effect is still possible.
“It could still have an effect given very early in disease, although less and less likely every day that passes,” Gellad said.
There are dozens of studies ongoing with hydroxychloroquine, more than for any other potential Covid-19 treatment, including studies that combine it with antibiotics such as azithromycin or doxycycline. But the results appear to show the benefit of putting resources into testing medicines in large randomized trials, the medical gold standard, during a pandemic.
The RECOVERY trial represented an early and large effort at such studies, testing not only hydroxychloroquine but also a pair of HIV drugs, lopinavir and ritonavir, and the steroid dexamethasone. The study was later expanded to also test using plasma from recovered patients to treat those who are still ill.