LONDON – After all the controversy and a huge dose of hype, there is no clinical benefit from the use of hydroxychloroquine in patients admitted to the hospital with COVID-19, according to headline data from a large randomized trial of potential drugs for the infection currently running in the U.K.
On June 5, the two chief investigators in the Recovery trial said the data “convincingly rule out any meaningful mortality benefit of hydroxychloroquine.”
A total of 1,542 patients were randomized to hydroxychloroquine and compared to 3,132 patients randomized to standard of care alone. There was no significant difference in the primary endpoint of 28-day mortality, with 25.7% of those in the active arm dying vs. 23.5% of patients receiving standard of care (p=0.10).
There was also no evidence of reduction in the length of hospital stay, or positive results for any other endpoints. There were no differences in response between male and female patients, or in different age groups.
“We have therefore decided to stop enrolling patients to the hydroxychloroquine arm of the Recovery trial with immediate effect,” said Peter Horby, chief investigator at Oxford University.
Horby said he spoke to the World Health Organization (WHO) on Friday to let it know of their findings, before the data were published. Earlier in the week, WHO resumed the hydroxychloroquine arm of its randomized Solidarity trial after a high-profile study in The Lancet showing increased mortality in patients treated with the drug was retracted.
In a briefing from its headquarters in Geneva, Soumya Swaminathan, WHO’s chief scientist, said the Solidarity trial will continue to randomize patients to be treated with hydroxychloroquine for now.
“We spoke to professor Horby, who informed us about the preliminary results. We await to see the final detailed analysis. Our data safety monitoring committee will be considering the results.” While Solidarity and Recovery are two of the largest studies and have similar designs, they are two distinct trials, Swaminathan said.
There has been “huge speculation and uncertainty” about the possible use of hydroxychloroquine, and an absence of reliable data, said Martin Landray, deputy chief investigator of the Recovery trial. “This result should change medical practice worldwide and demonstrates the importance of large randomized trials to inform decisions about both efficacy and safety,” Landray said.
WHO suspended the hydroxychloroquine arm of Solidarity at the end of May, after the meta-analysis published in The Lancet on May 22 purported to show COVID-19 patients treated with hydroxychloroquine had a higher mortality rate. Meanwhile, the data safety monitoring board for the Recovery trial reviewed the data and said patients in the U.K. could continue to be treated with the drug.
However, on June 4, the U.K. regulator, the Medicines and Healthcare products Agency, asked the committee to conduct a further review. The committee then told Horby and Landray to look at the unblinded data.
“We are now releasing the preliminary results as they have important implications for patient care and public health,” said Horby. “Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs,” he said.
Hydroxychloroquine was selected to be tested in the Recovery trial on the basis of in vitro data published in February showing it was effective against SARS-CoV-2. On the back of that, there were early reports from China suggesting there was benefit. The drug received further traction from uncontrolled data from France, while a number of small randomized trials reported positive effects.
Hydroxychloroquine was put forward for Recovery based on those data and because it is cheap and widely available, Horby said.
After all the hype and speculation, Landray said proving hydroxychloroquine doesn’t work is a significant result. “This is the end [of] a hypothesis. It is very important,” he said.
Given that, there are no regrets hydroxychloroquine was included in the Recovery trial, Landray said. “It was touted as a wonderful drug, as a breakthrough. It could have gone either way,” he told BioWorld. “Now people can stop using a drug that is useless.”
Peter Openshaw, professor of experimental medicine at Imperial College London, who is not involved in Recovery, agreed. “This is a really important result, at last providing unequivocal evidence that hydroxychloroquine is of no value in treatment of patients hospitalized with COVID-19.
“It’s quite toxic, so stopping treatment with this compound will be a great benefit to patients. The full results of the trial will take time to analyze and report, but it is a great credit to the investigators that they held on and continued the study despite the conflicting evidence from elsewhere,” Openshaw said.