As confirmed cases of Covid-19 approach 2 million, scientists are working tirelessly to find treatments and develop a vaccine for this respiratory illness. The message of what treatments have worked can appear confusing due to the relative infancy we are still in with regards to learning about the disease.
Amongst those treatments on trial is chloroquine – an anti-malarial drug that has received a lot of attention. However, its effectiveness as a treatment has been under further scrutiny, and now researchers of a small Brazilian study have reportedly stopped a group of patients receiving a high dose of chloroquine after some developed heart arrhythmias.
Eighty-one participants enrolled in the trial received different doses of chloroquine to test whether it was a safe and effective treatment for Covid-19. The “double-blind” study meant that neither patient nor doctor knew who was receiving a “high dose” of the drug, which consisted of 600 milligrams twice daily for 10 days, or a “low dose” of 450 milligrams for five days, including a double dose on the first day. This was in addition to drugs administered per hospital protocol, including the antibiotic drug azithromycin.
As described in the paper on the pre-print server medrXiv (not yet peer-reviewed), several days into the trial researchers noticed heart arrhythmias in patients taking the higher dose, and by day six, 11 patients had died. This warranted the immediate interruption of the high-dose arm of the trial, and the remaining patients unmasked and reverted to the low-dose arm. Yet even then, there were not enough patients included in the low-dose branch to determine whether chloroquine was effective in patients with severe disease.
“To me, this study conveys one useful piece of information, which is that chloroquine causes a dose-dependent increase in an abnormality in the ECG [electrocardiogram] that could predispose people to sudden cardiac death,” Dr David Juurlink, an internist and the head of the division of clinical pharmacology at the University of Toronto, told The New York Times.
In a similar vein, the American College of Cardiology recently published a new guidance warning that the combination of hydroxychloroquine (the hydroxylated version of chloroquine) and azithromycin might heighten some patients' risk of experiencing potentially fatal irregular heartbeats, a factor that has caused at least one patient to drop out of another hydroxychloroquine trial in France after it became a “major risk” to their cardiac health.
Multiple studies of the anti-malarial drugs, which are also used to treat lupus, have appeared across the globe. Last month, the World Health Organization (WHO) announced it would include the pair in their global megatrial due to the “significant attention” that the drugs have received in several countries, including from President Trump, which “prompted the need to examine emerging evidence to inform a decision on its potential role.”
On a smaller scale, a study in China and a study in France both found that the use of hydroxychloroquine proved effective to small groups of patients with mild symptoms, although there are several limitations with both studies. In fact, two other studies, also from China and France, found that hydroxychloroquine was no better for treating Covid-19 than current conventional care. In spite of this, the FDA recently approved the use of the two drugs for emergency use to treat Covid-19.
Writing in an article for The Conversation, Katherine Seley-Radtke, professor of Chemistry and Biochemistry and president-elect of the International Society for Antiviral Research, University of Maryland, Baltimore County, underscored the importance of waiting for larger scale evidence of the drugs’ capabilities as a treatment to assess its effectiveness and safety: “Despite the recent approval of this drug for use against Covid-19, questions remain as to the efficacy of this treatment. As Molina and colleagues note: 'Ongoing randomized clinical trials with hydroxychloroquine should provide a definitive answer regarding the alleged efficacy of this combination and will assess its safety.””