Big UK trial says hydroxychloroquine has no effect on COVID-19

The largest trial to date on hydroxychloroquine has concluded it has “no beneficial effect” when used to treat patients hospitalised with COVID-19.

As a consequence the multidrug RECOVERY trial – by University of Oxford researchers led by Professors Peter Horby and Martin Landray – will stop enrolling patients in the hydroxychloroquine arm, but will continuing treating subjects in the other five arms.

The 11,000-patient study comes on the back of a drip-feed of negative clinical results with the anti-malarial drug in coronavirus from smaller trials in coronavirus patients.

Last week, for example, a study also found that hydroxychloroquine had no benefit when used prophylactically in patients exposed to someone with an active coronavirus infection, while an earlier Chinese study in the British Medical Journal found no benefit in COVID-19 patients admitted to hospital with persistent mild to moderate symptoms.

In RECOVERY, 1,542 patients were treated with hydroxychloroquine and compared to more than 3,000 patients given standard care. There was no difference between the groups on the main endpoint of mortality at 28 days – which came in at 25.7% with the drug and 23.5% for standard care.

There was also no benefit on secondary outcome measures like hospital stay duration, according to the Oxford team.

As a prospective randomised controlled trial including more than 1,500 people on hydroxychloroquine RECOVERY’s failure is a real blow to the drug’s prospects, although a couple of other trials are still putting the drug through its paces.

The World Health Organization (WHO) has just restarted the hydroxychloroquine arm of its SOLIDARITY trial, which had been suspended following a study published in The Lancet that suggested the drug was linked to a higher risk of ventricular arrhythmias and patient mortality when used to treat COVID-19 patients.

Last week however three of that article’s authors took the remarkable step of retracting the study, saying they could not “vouch for the veracity” of the data – generated by Surgisphere Corp – because the company had refused to make it available for an independent audit.

The study examined the records of almost 15,000 patients treated with hydroxychloroquine or related drug chloroquine, and generated headlines around the world when it was published, particularly when it emerged President Donald Trump had been taking the drug prophylactically to ward off coronavirus.

SOLIDARITY is also comparing hydroxychloroquine and other drugs to standard care in patients hospitalised for COVID-19.

Another big study – called COPCOV – is testing Trump’s hypothesis that taking hydroxychloroquine before exposure to the virus may protect from infection.

The Mahidol Oxford Tropical Medicine Research Unit (MORU), based in Bangkok, Thailand, is leading the 40,000-patient study, with UK sites including Brighton and Sussex University Hospitals and the John Radcliffe Hospital in Oxford.