Virus World

A research trial of coronavirus patients in Brazil ended after patients taking a higher dose of chloroquine, one of the drugs President Trump has promoted, developed irregular heart rates. A small study in Brazil was halted early for safety reasons after coronavirus patients taking a higher dose of chloroquine developed irregular heart rates that increased their risk of a potentially fatal heart arrhythmia.

Chloroquine is closely related to the more widely used drug hydroxychloroquine. President Trump has enthusiastically promoted them as a potential treatment for the novel coronavirus despite little evidence that they work, and despite concerns from some of his top health officials. Last month, the Food and Drug Administration granted emergency approval to allow hospitals to use chloroquine and hydroxychloroquine from the national stockpile if clinical trials were not feasible. Companies that manufacture both drugs are ramping up production.

The Brazilian study involved 81 hospitalized patients in the city of Manaus and was sponsored by the Brazilian state of Amazonas. It was posted on Saturday at medRxiv, an online server for medical articles, before undergoing peer review by other researchers. Because Brazil’s national guidelines recommend the use of chloroquine in coronavirus patients, the researchers said including a placebo in their trial — considered the best way to evaluate a drug — was an “impossibility.” Despite its limitations, infectious disease doctors and drug safety experts said the study provided further evidence that chloroquine and hydroxychloroquine, which are both used to treat malaria, can pose significant harm to some patients, specifically the risk of a fatal heart arrhythmia. Patients in the trial were also given the antibiotic azithromycin, which carries the same heart risk. Hospitals in the United States are also using azithromycin to treat coronavirus patients, often in combination with hydroxychloroquine.

Preprint of the Study available in medRxiv (April 11, 2020):

https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1

President Donald Trump has touted the drug as a treatment but scientists still don't know for sure that it is effective in patients. A number of clinical trials aim to find out. On March 16, SpaceX founder Elon Musk tweeted that the anti-malaria drug chloroquine was “maybe worth considering” as a treatment for COVID-19. He got 13,000 retweets. By March 19, President Donald Trump was touting chloroquine at a press conference. He even announced that the Food and Drug Administration had fast-tracked its approval for COVID-19. The FDA denied that this was the case a short time later. While some of the hype has been fuelled by a document generated outside the scientific literature, chloroquine’s potential in treating COVID-19 is gaining traction in the medical community. The drug has a long track record in medicine, having been used since the 1940s as an antimalarial. The modern drug is made from the bark of the Cinchona plant, which was taken as an herbal remedy by indigenous Peruvians four centuries ago to treat fever. And there are some early indications it could work against SARS-CoV-2 infections.

For instance, a study in France published on March 20 in the International Journal of Antimicrobial Agents described the treatment of 42 patients hospitalized with COVID-19, 26 of whom received a version of chloroquine called hydroxychloroquine and 16 of whom received routine care. Of the 20 patients who took the antimalarial and completed the study, six also received azithromycin, an antibiotic. All six of these patients were free of SARS-CoV-2 by the fifth day post-treatment, while seven of 14 patients who took hydroxychloroquine alone were negative for the virus, and two of 16 control patients were no longer infected. Small-scale experiments in which chloroquine has been given to COVID-19 patients in China and Australia have also shown encouraging results as far as shortening the course of the disease. A small trial of 1,500 people would be a pragmatic step towards verifying the drug’s efficacy, says Jeremy Rossman, a virologist at the University of Kent, who praises the approach. 

A number of other chloroquine experiments on humans are in the works. According to clinicaltrials.gov, researchers at the University of Oxford plan to give it as a prophylactic to 10,000 health care workers and others at high risk of contracting SARS-CoV-2. In Norway, doctors expect to begin administering the drug to hospitalized patients. And in Thailand, clinicians are preparing for a clinical trial comparing various combinations of antivirals, including chloroquine.