Hydroxychloroquine does not work against Covid-19 and should not be given to any more hospital patients around the world, say the leaders of the biggest and best-designed trial of the drug, which experts will hope finally settle the question.
“If you are admitted to hospital, don’t take hydroxychloroquine,” said Martin Landray, deputy chief investigator of the Recovery trial and professor of medicine and epidemiology at Oxford University. “It doesn’t work.”
Many countries have permitted emergency use of the drug for Covid-19 patients in hospitals, following claims from a few doctors, including Didier Raoult in France, that it was a cure, and the ensuing clamour from the public. President Donald Trump backed the drug, saying it should be given to patients, and later said he was personally taking it to protect himself from the virus.
Hydroxychloroquine, also known by its brand name, Plaquenil, is a drug used to treat malaria. It is a less toxic version of chloroquine, another malaria drug, which itself is related to quinine, an ingredient in tonic water.
A widely publicized study in France where 40 coronavirus patients were given hydroxychloroquine, with more than half experiencing the clearing of their airways within three to six days has led to it being touted in some quarters as a potential cure for Covid-19. This apparent improvement is important as it would curtail the timeframe in which infected people could spread Covid-19 to others.
However, experts have warned that the study is small and lacks sufficient rigour to be classed as evidence of a potential treatment. The French study followed work by Chinese researchers which suggested that hydroxychloroquine can slow infections by blocking the virus behind Covid-19 from entering cells in the body. But more recent, albeit small-scale, research from China has shown that patients who were treated with the drugs fought off coronavirus no more quickly than those who didn’t get it. Indeed, one patient given hydroxychloroquine severely worsened in condition while four patients on the medicine developed signs of liver damage and experienced diarrhoea. US president Donald Trump has claimed he takes hydroxychloroquine despite FDA warnings.
Here is a guide to the scientific studies into hydroxychloroquine and coronavirus carried out so far.
Regardless of these findings, any drug being used for a certain purpose before full clinical trials are completed is, by definition, untested and unproven. It’s too early to say if hydroxychloroquine can have a major benefit or not. The European Medicines Agency, an agency of the EU, has said hydroxychloroquine should not be taken by coronavirus patients except for clinical trials or emergency use programs.
Landray said the hype should now stop. “It is being touted as a game-changer, a wonderful drug, a breakthrough. This is an incredibly important result, because worldwide we can stop using a drug that is useless.”
The first results from the Recovery trial, which has been testing seven therapies for Covid-19, swiftly followed the retraction of a paper in the Lancet medical journal on Thursday night claiming that hydroxychloroquine was linked to an increased risk of death in Covid-19 patients. The authors of the paper withdrew it after the US company Surgisphere refused to cooperate with an independent audit of the data it had supplied for the study. A Guardian investigation had showed serious errors in the data and raised questions about Surgisphere and its CEO.
Supporters of the drug hailed the paper’s retraction, but the World Health Organization and countries that have authorised use of the drug are now likely to change their position.
The Recovery trial is a “gold standard” randomised controlled trial, designed to find an answer to a question by recruiting patients in similar circumstances either to take the drug or to take a placebo. Their doctors and the researchers do not know which ones are taking the genuine trial drug.
Because of the furore over the Lancet paper, the Medicines and Healthcare Products Regulatory Agency asked the trial’s independent monitoring board to look at the latest data. The board revealed the findings to the researchers, recommending that the hydroxychloroquine arm of the trial should be stopped.
Since March, when the trial began, a total of 1,542 patients had been randomised to receive hydroxychloroquine, while 3,132 patients were randomised to receive only normal care. Over 28 days, 25.7% of patients on hydroxychloroquine died, compared with 23.5% of the others. The difference is not statistically significant – it could have arisen by chance. But the clear conclusion was that hydroxychloroquine did not work, said the researchers.
Peter Horby, professor of emerging infectious diseases and global health at the University of Oxford, said they had informed the WHO, which had just restarted its hydroxychloroquine trials after pausing them because of the Lancet paper. That was an observational study – comparing patients in hospitals who happened to have been treated with the drug with others who had not.
“One of the key lessons we should learn historically is that making treatment decisions based on observational data is not the way forward,” he said.