Study Examining Higher Chloroquine Doses in COVID-19 Halted Early Due to Safety Concerns
A study based in Brazil has been halted early for safety reasons after patients with coronavirus disease 2019 taking a higher dose of chloroquine developed irregular heart rates that increased their risk of a potentially fatal heart arrhythmia.
A study based in Brazil has been halted early for safety concerns after patients with coronavirus disease 2019 (COVID-19) taking a higher dose of chloroquine (CQ) developed irregular heart rates that increased their risk of a potentially fatal heart arrhythmia.1
Antimalarial drugs CQ and hydroxychloroquine (HCQ) have been touted as potential treatments for COVID-19, although experts have issued concerns of global supply shortages. Last month, the FDA granted emergency approval to allow hospitals to use HCQ and CQ from the national stockpile if clinical trials were not feasible.
According to the study, this is the first double-blinded, randomized clinical trial addressing different dosages of CQ for the treatment of severe patients with COVID-19 in the absence of a control group using placebo. The study included 81 hospitalized patients in the city of Manaus. Because Brazil’s national guidelines recommend the use of chloroquine in patients with COVID-19, the researchers said including a placebo in their trial was not possible.2
Researchers performed a parallel, double-blinded, randomized, phase 2b clinical trial aimed to assess the safety and efficacy of 2 different CQ dosages as adjunctive therapy of hospitalized patients with severe acute respiratory syndrome (SARS). Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600 mg CQ twice daily for 10 days) or low dose CQ (450 mg for 5 days).2
Infectious disease doctors and drug safety experts noted that the study provided further evidence that antiviral medications HCQ and CQ can pose significant harm to certain patients, particularly with regards to the risk of fatal heart arrhythmia. Participants were also given the antibiotic azithromycin, which carries the same heart risk.2
“The preliminary findings from CloroCovid-19 trial suggest that the higher dosage of CQ (12 g total dose over 10 days) in COVID-19 should not be recommended because of safety concerns regarding QTc prolongation and increased lethality, in the Brazilian population, and. more often in older patients in use of drugs such as azithromycin and oseltamivir, which also prolong QTc interval,” the study authors wrote.2
In recent weeks, pharmaceutical companies such as Novartis and Rising Pharmaceuticals have supported clinical trials exploring HCQ as a treatment for COVID-19, adding that they have donated more than 200,000 doses of HCQ to the University of Washington for a COVID-19 PEP clinical trial.
Additionally, several clinical trials for chloroquine and hydroxychloroquine are testing low doses for shorter periods of time in patients with the coronavirus. But the Health Commission of Guangdong Province in China had initially recommended those sick with the virus be treated with 500 milligrams of chloroquine twice daily for 10 days1.
Study author Marcus Lacerda, MD, told The New York Times that his study found that “the high dosage that the Chinese were using is very toxic and kills more patients.1”
The researchers concluded that the study did not include enough participants in the lower-dose portion of the trial to conclude whether CQ was effective in patients with severe disease. More studies evaluating the drug earlier in the course of the disease are “urgently needed,” according to the researchers.1
- Thomas, Katie; Sheikh, Knvul. Small Chloroquine Study Halted Over Risk of Fatal Heart Complications. New York Times. Published April 12, 2020. https://www.nytimes.com/2020/04/12/health/chloroquine-coronavirus-trump.html?auth=login-email&login=email. Accessed April 13, 2020.
- Silva Borba, M.G.; Almeida Val, F.F.; Sampaio, V.S. et al. Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study). MedRxiv website. Published April 12, 2020. https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.full.pdf. Accessed April 13, 2020.
- Request for Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease. FDA website. Published March 28, 2020. https://www.fda.gov/media/136534/download. Accessed April 13, 2020.