Medicines

Hydroxychloroquine trial controversy continues


Editors note: This story has been updated on 4/6/2020 to reflect study retractions:

The World Health Organization has now resumed the SOLIDARITY trial of hydroxychloroquine after previously suspending it over safety concerns raised in a now retracted Lancet paper.

WHO had earlier suspended the hydroxychloroquine arm of the SOLIDARITY trial in patients with COVID-19 after a controversial study found that the drug was linked with an increased risk of heart arrhythmias and death.

However Australian researchers said they will continue with their trial of the drug as a preventive agent for healthcare workers potentially exposed to COVID-19.

Published in the Lancet, the disputed observational study included more than 96 000 patients admitted to hospital with COVID-19 across six continents, of whom 1868 received chloroquine, 3783 chloroquine with a macrolide, 3016 hydroxychloroquine, and 6221 who received hydroxychloroquine with a macrolide. Meanwhile, 81 144 patients were in the control group.

After controlling for multiple confounding factors, 9.3% of patients in the control group died in hospital compared to 18% of those treated with hydroxychloroquine alone, 16.4% of patients treated with chloroquine alone,  22.2% of those treated with chloroquine and a macrolide and 23.8% of those treated with hydroxychloroquine and a macrolide.

And compared with the control group, patients treated with any of the treatment regimens had a higher risk of de-novo ventricular arrhythmias, with the biggest increase in risk seen in patients treated with hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

In light of the findings, the WHO initially said it had decided to implement a temporary pause of the hydroxychloroquine arm within the SOLIDARITY trial as a precaution while the safety data was being reviewed.

However the Lancet has now retracted the study after concerns were raised about the validity of the database provided by a private analytic company Surgisphere.

“Three of the authors of the paper … have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they ‘can no longer vouch for the veracity of the primary data sources’,” the Lancet said in a statement

Researchers at the Walter and Eliza Hall Institute of Medical Research in Melbourne said their COVID SHIELD trial of hydroxychloroquine as preventive treatment would continue, noting that it was different from treatment trials that used higher doses of hydroxychloroquine.

Another study, published in the NEJM, that relied on Surgisphere data has also been retracted. The NEJM study had found that drugs acting on the angiotensin system such as ACE inhibitors did not increase the risk of death in COVID-19 patients.

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