番茄社区

No indication of survival benefit was found for hydroxychloroquine (HCQ) in hospitalized COVID-19 patients in a large randomized trial, according to .

There was no significant difference in 28-day mortality with HCQ versus usual care -- and in fact trended toward increased risk of death with the active drug (25.7% for HCQ vs 23.5% for usual care, HR 1.11, 95% CI 0.98-1.26, P=0.10, according to a statement from the study's leaders.

Moreover, the drug had no beneficial effect on "hospital stay or duration or other outcomes" in the , the statement said.

Based on these data, no more patients will be enrolled in the HCQ arm. The will continue with respect to other study arms, which, besides HCQ, include five other agents: tocilizumab (Actemra), convalescent plasma, azithromycin, low-dose dexamethasone, and lopinavir/ritonavir (Kaletra), as well as usual care.

More than 11,000 patients have been enrolled in 175 hospitals across Britain; 1,542 were assigned to HCQ and 3,132 to usual care.

The study leaders' statement said Great Britain's Medicines and Healthcare Products Regulatory Agency -- equivalent to the FDA in the U.S. -- asked the trial's independent data monitoring committee to review the trial's data, which it did on Thursday. That group then recommended that the chief investigators examine the unblinded data, and a decision was reached to stop enrolling patients in the HCQ trial arm immediately and release the preliminary results. (Although treating physicians and patients were not blinded to treatment assignments, the chief investigators did not have access to allocations or outcomes data while the study was underway, .)

The investigators' statement did not mince words, stating, "These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients [hospitalized] with COVID-19."

Deputy chief investigator Martin Landray, PhD, of the University of Oxford in England, went further: "This result should change medical practice worldwide." He noted it demonstrated the importance of large, randomized trials to inform decisions about treatments' safety and efficacy.

The statement promised that full results would be "made available as soon as possible."

Matthew Spinelli, MD, of the University of California San Francisco, who was not involved with the research, characterized the results as "pretty definitive" in hospitalized patients with COVID-19.

"It's quite a large trial with a tight confidence interval in a sick patient population," he told 番茄社区. "This is an example of the appropriate study design to assess the impact of mortality, with much higher quality of evidence" than an observational study.

Noting the recently published trial examining HCQ as post-exposure prophylaxis -- which also found no benefit for the drug -- Spinelli said there are still ongoing studies of the drug as prevention, but "there's not much of a signal that it works."

"It's never struck me as a very promising drug. It's shown in vitro effects on a lot of viruses and hasn't panned out for any of them," he said. "I was never particularly hopeful for it, but I wouldn't have written it off based on that. I was waiting for a randomized trial to give us this answer."

RECOVERY trial chief investigator Peter Horby, MD, PhD, also of the University of Oxford, said in the group's statement that while it's disappointing the treatment was ineffective, "it does allow us to focus care and research on more promising drugs."

Spinelli said he worries that, due to the politicized environment around HCQ, "many duplicative trials will be done."

"If we don't think the drug is going to work, then the equipoise is gone and it's likely not benefiting people in a trial. Other trials with similar designs in hospitalized patients should consider convening their data safety and monitoring boards."

The investigators said full results will be made available as soon as possible.

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