A Brazilian study investigating whether the anti-malaria drug chloroquine was effective in treating patients with Covid-19 was halted on safety concerns, after a high dose of the drug proved lethal for some patients.

Chloroquine, and a related drug, hydroxychloroquine, in combination with the antibiotic azithromycin, has been touted as a potential treatment for coronavirus by Donald Trump despite a lack of evidence.

The findings were published as a letter in the journal Nature raised alarm about serious heart risks associated with Covid-19 patients taking the drugs and the US Food and Drug Administration warned of serious heart complications.

Donald Trump has previously urged Americans to take hydroxychloroquine, although he has apparently backed away from the drug in recent days, and on Thursday even suggested that injections of disinfectant could cure Covid-19 – an idea that was swiftly refuted by experts, who warned the public “please don’t inject bleach”.

The Brazilian study, published in the Journal of the American Medical Association Network Open (Jama), was halted by a safety monitoring board before even one-quarter of the planned 440 patients were enrolled. Eighty-one patients with Covid-19 or suspected Covid-19 were given a daily regimen of chloroquine. The randomized clinical trial separated the patients into a high-dose and a low-dose group.

Researchers planned to assess their outcomes after 28 days.

But after 13 days, six of 40 patients in the low-dose group had died, compared with 16 of 41 patients in the high-dose group. Furthermore, five patients in the high-dose group had underlying heart disease, three of whom died.

“Despite these discouraging findings, several other observations prevent concluding categorically that high-dose chloroquine was toxic,” authors of a comment article said.

Hydroxychloroquine and chloroquine in combination with azithromycin were first put forward as potential treatments for Covid-19 in a French study described as “meaningless”. The journal later said the study did not meet standards for publication.

But by the time the journal disavowed the study’s flawed design, media outlets had already promoted the unproven and risky drug combination. The treatment was tweeted by the tech billionaire Elon Musk and picked up by Fox News. It was then touted by Trump as a potential “game-changer” despite serious risks and lack of safety and efficacy data. At least one man has died and a woman was hospitalized after taking chloroquine.

The letter published in Nature warned of serious heart problems and risk of “sudden cardiac death” in patients treated with hydroxychloroquine and azithromycin.

In the letter, which unlike a study is not peer-reviewed, a New York City doctor described 84 Covid-19 patients’ reaction to a five-day, twice-daily regimen of the drugs. The patients were monitored on electrocardiogram. Both drugs have independently been shown to increase patients’ risk of “drug-induced sudden cardiac death”.

Among the 84 patients, nine showed signs of potentially severe heart “malignant arrhythmia” which could increase risk of cardiac arrest, although none had heart attacks. At the end of the study, four patients had died of multi-organ failure, 16 patients were discharged and another 64 remained in hospital. The authors concluded patients on the regimen need to be “constantly monitored” for heart problems.

Despite the lack of evidence that it is an effective treatment for Covid-19, some American hospitals have used hydroxychloroquine to treat seriously ill patients in the hope of some benefit.

However, scientists have repeatedly urged caution. The American Thoracic Society (ATS) and the Infectious Diseases Society of American have both called for the drug to be used only in clinical trials.

In clinical guidelines to doctors, Dr Kevin C Wilson, chief of documents and patient education at the ATS, said that while some lab results showed antiviral effects against the virus, they have yet to be replicated with patients.

“Thus, the bottom line is, whether hydroxychloroquine and chloroquine confer benefits to patients with Covid-19 are unanswered questions.”