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01-05-2020 | COVID-19 | News

CloroCovid-19 results reinforce the need for caution with chloroquine, hydroxychloroquine use

Author: Claire Barnard


medwireNews: Findings from the phase 2b CloroCovid-19 trial indicate that patients with severe suspected COVID-19 who are treated with high-dose chloroquine have higher rates of death than those given low-dose chloroquine.

These findings suggest “that high-dose chloroquine (and by close association, hydroxychloroquine) […] is potentially associated with increased mortality,” say Stephan Fihn (University of Washington, Seattle, USA) and co-authors in an editorial accompanying the research published in JAMA Network Open.

The trial included 81 hospitalized patients with severe respiratory syndrome and clinical suspicion of COVID-19 who were randomly assigned to receive high-dose (600 mg twice daily for 10 days) or low-dose (450 mg twice daily on day 1 and once daily for 4 days) chloroquine treatment. All patients received concomitant treatment with the antibiotic azithromycin, while 92.5% and 86.8% of patients in the high-dose and low-dose groups, respectively, received the antiviral medication oseltamivir due to suspected influenza.

The CloroCovid-19 investigators, led by Marcus Lacerda (Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil), found that 39% of the 41 patients given high-dose chloroquine died over 13 days of follow-up, compared with just 15% of the 40 participants in the low-dose group, translating into a significant 3.6-fold elevated risk for death with the high dose.

In an exploratory multivariate analysis, the researchers found that this association was attenuated to 2.8-fold, and no longer statistically significant, after controlling for age, suggesting that “[a]ge was an important confounder and might be associated with the unfavorable outcomes.”

Patients in the high-dose group were also more likely than those in the low-dose group to have a QTc interval corrected by the Fridericia method of greater than 500 milliseconds (18.9 vs 11.1%), while two (2.7%) patients in the high-dose group experienced ventricular tachycardia, compared with none in the low-dose group.

These “preliminary findings” suggest that “higher dosage of chloroquine should not be recommended for the treatment of severe COVID-19, especially among patients also receiving azithromycin and oseltamivir,” say Lacerda and team.

The editorialists believe that the CloroCovid-19 findings “should prompt some degree of skepticism toward the enthusiastic claims about chloroquine and perhaps serve to curb the exuberant use.”

However, Fihn (University of Washington, Seattle, USA) and co-authors say that a number of factors “prevent concluding categorically that high-dose chloroquine was toxic and that the likely mechanism was arrhythmogenesis.” For instance, there was “no witnessed torsade de pointes, an arrhythmia that is characteristically induced by QTc interval prolongation,” and treatment with azithromycin and oseltamivir “can also prolong the QTc interval,” they say.

They add that “[s]everal other trials, including a large multicenter trial in the US, are ongoing and hopefully will provide additional crucial information about the efficacy and safety of hydroxychloroquine.”

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

1 May 2020: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

JAMA Network Open 2020; 3: e208857
JAMA Network Open 2020; 3: e209035