Hydroxychloroquine: WHO resumes trials for coronavirus treatment

New research suggests a controversial drug being pushed as a potential COVID-19 treatment by Donald Trump doesn’t work anyway.

The World Health Organisation has ended a pause on trials of a controversial drug being pushed as a potential COVID-19 therapeutic by US President Donald Trump, as separate research shows it probably doesn’t do anything anyway.

The WHO first announced a pause on trials for the drug hydroxychloroquine last week following a study published in the Lancet medical journal.

That study reported that patients who received the drug had a higher estimated mortality rate.

Following that study, WHO director-general Dr Tedros Adhanom Ghebreyesus announced that the Solidarity Trial, an international clinical trial by the WHO and partnering countries aimed at finding an effective treatment for COVID-19, would pause trials of hydroxychloroquine.

The Executive Group of the #COVID19 Solidarity Trial met on Saturday to review a study on hydroxychloroquine and decided to temporarily pause this arm of the trial while data is reviewed. https://t.co/tk7iHMfAza

— Tedros Adhanom Ghebreyesus (@DrTedros) May 26, 2020

The Solidarity Trial involves more than 400 hospitals in 35 countries that are actively recruiting patients.

Nearly 3500 patients have been enrolled from 17 countries.

The pause on hydroxychloroquine trials was supposed to give time for the Data Safety Monitoring Board to review safety data, but during that time the Lancet study that prompted the decision came under a cloud.

The data used in the study purportedly came from more than 96,000 patients in 671 hospitals around the world, but appears seriously flawed.

French medicine professor Didier Raoult has been at the forefront of promoting hydroxychloroquine as a potential treatment for COVID-19. His methodology has also been criticised. Picture: Christophe Simon/AFP

Firstly, the company that mysteriously came to possess the data couldn’t explain where it got it from, and it appears it didn’t know how to use it either.

In one particular highlight, the data, from only five hospitals, claimed that 73 Australians had died from COVID-19 on April 21, when only 67 deaths had been recorded here.

An Asian hospital included in our tally by mistake has been blamed for the discrepancy.

The WHO will resume investigating whether hydroxychloroquine is useful in treating COVID-19. Picture: George Frey/AFP

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Seven hospitals in Australia also denied having anything to do with the company that supposedly collected the data.

Both the Lancet and the New England Medical Journal, which published an earlier study on blood pressure drugs being used to treat COVID-19 by the same authors, have expressed their concern about the data used but are yet to issue retractions.

We have published an Expression of Concern on the paper by Mehra et al on hydroxychloroquine and chloroquine published on May 22, 2020 https://t.co/yQ9irhRHxx pic.twitter.com/5I1NXTKTjo

— The Lancet (@TheLancet) June 2, 2020

According to The Guardian, the “tiny US company” Surgisphere held data that was used in the study, which was co-authored by Surgisphere CEO Sapan Desai.

But the company hasn’t been able to explain the data or how it was interpreted.

The study authors (excluding the ones with links to Surgisphere) are now undertaking an audit of the data, seeking to find out where it came from and whether it’s valid.

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US President Donald Trump shocked reporters with the news he was taking the drug last month. Picture: Evan Vucci/AP

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The Guardian also reported several Surgisphere employees had no data or scientific background, including a science fiction author who acts as the company’s science editor, and an “adult-content model” who acts as a company marketing executive.

Following review by its Data Safety Monitoring Board, the WHO has given the green light for trials of hydroxychloroquine to resume, now of the opinion it’s not nearly as deadly as the apparently flawed study suggested.

Based on available data, the #COVID19 Solidarity Trial Data Safety & Monitoring Committee recommended there are no reasons to modify the trial protocol. The Executive Group endorsed the continuation of all arms of the Trial, including the use of hydroxychloroquine. https://t.co/r88DVEvZ3j pic.twitter.com/cYITShxcE7

— Tedros Adhanom Ghebreyesus (@DrTedros) June 3, 2020

But while the drug may not be deadly, it doesn’t appear to do much to treat COVID-19.

A new study, led by University of Minnesota researchers, separate from the WHO’s trial and published in the New England Medical Journal, reports hydroxychloroquine is no more effective than a placebo.

In this double-blind, randomized trial, 821 asymptomatic persons with a high- or moderate-risk exposure to #SARSCoV2 were assigned to receive hydroxychloroquine or placebo within 4 days after the exposure. No benefit in preventing illness compatible with #COVID19 was found.

— NEJM (@NEJM) June 3, 2020

The double-blind study (only the pharmacies that distributed the real drugs and placebos knew which patients got which ones) used a more manageable sample size of 821 people.

None of them had COVID-19 symptoms when the trial began, but 719 of them reported they’d had “high-risk exposure” to a confirmed infected person within the previous four days.

Patients were then randomly assigned either a course of hydroxychloroquine, or a placebo.

49 out of the 414 who received the real drug and 58 out of 407 who received the placebo were either confirmed to have COVID-19 in a lab test, or had “illness compatible with COVID-19”, within 14 days.

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The WHO will resume trialling hydroxychloroquine as a COVID-19 treatment, but a new study suggests it’s wasting its time. Picture: George Frey/AFP

Those who’d taken the real drug experienced more side effects, but no seriously adverse reactions were reported by either group.

The study authors concluded that hydroxychloroquine “did not prevent illness compatible with COVID-19 or confirmed infection when used as post-exposure prophylaxis within four days after exposure”.

Lead author David Boulware told Wired magazine the drug essentially did nothing.

“There was no effect. There was no statistical difference between those who got hydroxychloroquine and those who did not,” he said, adding that the results were “disappointing, but perhaps not surprising”.

Pharmaceutical and biotechnology industry consultant and honorary senior fellow at the University of Melbourne Dr Phillip Reece explained the difficulty drug trials are having responding to COVID-19.

“The urgency of the situation has put pressure on usual drug development pathways through a need to identify effective antivirals as quickly as possible without compromising safety,” he said.

He added that using hydroxychloroquine to treat COVID-19 offered benefits because it was already approved and on the market to treat other diseases.

“However, even in this case, precaution is warranted as the safety profile could be different in patients with COVID-19. Differences in dose size, dose frequency or duration for the new indication will further complicate the situation and change the safety profile,” Dr Reece said.

“The rapid pace of the COVID outbreak means that the early data we collect may be misleading or incomplete,” University of Adelaide senior medicine lecturer Dr Ian Musgrave said.

“While hydroxychloroquine has been given undue attention (and its potential harms minimised) there may still be some benefit to its judicious use,” he said.

“The Lancet case shows us that the scientific community must remain vigilant even with results we agree with and that data transparency and data sharing are even more important when we need to make good conclusions quickly in uncertain times.”