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(Longhua Liao/Getty Images)

Study of High-Dose Chloroquine For COVID-19 Stopped Early Due to Patient Deaths

JACINTA BOWLER
14 APRIL 2020

As the pandemic continues to rage across the globe, one potential treatment researchers are investigating for COVID-19 is the malaria drug chloroquine. But concerning early results from a clinical trial in Brazil now add to the growing suspicion this could be far from the silver bullet we're looking for.

 

Chloroquine came onto the scene as a potential MERS treatment back in 2012, but was not investigated further because it didn't show enough activity against the virus. Recently, small studies have picked up that line of investigation again, looking into whether the drug could block coronaviruses such as COVID-19 from infecting cells.

The antimalarial is known to cause dangerous side-effects; even its relatively 'safer' cousin, hydroxychloroquine, doesn't have a great track record. Of particular concern is the risk for patients to develop serious heart problems.

"The antimalarial medication hydroxychloroquine and the antibiotic azithromycin are currently gaining attention as potential treatments for COVID-19, and each have potential serious implications for people with existing cardiovascular disease," the American Health Association notes in a statement.

"Complications include severe electrical irregularities in the heart such as arrythmia (irregular heartbeat), polymorphic ventricular tachycardia (including Torsade de Pointes) and long QT syndrome, and increased risk of sudden death."

The latest research to add to these worries is a clinical trial from Brazil. The team released their preliminary results on the pre-print server medRxiv when they stopped the high-dose arm of their study after just six days, as several patients died - especially in the group randomised to receive higher doses of the drug.

 

The researchers enrolled two groups of COVID-19 patients in a public hospital in Manaus; the high-dose group was assigned a total dose of 12 grams of chloroquine over 10 days, while the low-dose group took a total dose of 2.7 grams over 5 days. All participants also received the antibiotics ceftriaxone and azithromycin.

After 11 patients died across both dosage groups, the team halted the high-dose arm of the trial on day six, citing more heart rhythm problems in the high-dose group, and "a trend toward higher lethality".

"Preliminary findings suggest that the higher chloroquine dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm," the team concludes in the pre-print.

In a later update revealed to CNN, the researchers noted that they experienced even more deaths in the high-dose group than were documented on day six. And it doesn't mean the low-dose group is safe, either.

"The major difference between the high-dose and the low-dose group occurred during the first three days and the actual toxicity - two patients in the high-dose chloroquine arm developed ventricular tachycardia before death," Vanderbilt University infectious disease researcher William Schaffner, who was not involved in the study, told CNN.

"So, it's clear that the high-dose group was more toxic, but it's not as though the low-dose group was without concern, and in larger studies you might find some problems with the low-dose group as well."

These worrying results come after a hospital in France also stopped a trial of hydroxychloroquine due to side effects and risk of heart damage, and similar small studies have found little difference in COVID-19 patients treated with a combination of the malarial drug and the antibiotic; the latter carries a risk of heart rhythm side-effects even by itself.

The research team in Brazil moved all of the remaining patients to the low-dose arm of the trial in compliance with a recommendation from the Data Safety and Monitoring Board. Additionally, they recommend more trials to evaluate the role chloroquine might play in COVID-19 treatment and prophylaxis - much-needed data that could benefit us all in the future.

"Even if we fail to generate good evidence in time to control the current pandemic, the information will highly impact the way we deal with next coronavirus outbreaks in the future," the team writes in the pre-print.

The research is available on medRxiv.