Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

The objective of this parallel, double-masked, randomized, phase IIb clinical trial, was to evaluate the safety and efficacy of 2 chloroquine diphosphate (CQ) dosages in patients with severe COVID-19. 81 adult patients who were hospitalized with SARS-CoV-2 infection were enrolled from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.

The objective of this parallel, double-masked, randomized, phase IIb clinical trial, was to evaluate the safety and efficacy of 2 chloroquine diphosphate (CQ) dosages in patients with severe COVID-19. 81 adult patients who were hospitalized with SARS-CoV-2 infection were enrolled from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). The primary outcome of the study was the reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented in the study refer primarily to safety and lethality outcomes during treatment on day 13. Concerning the results, the authors found that the lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group exhibited  more cases of prolonged  QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. However, the authors underline that these findings cannot be extrapolated to patients with non-severe COVID-19.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765499

by Marialuisa Zedde and Francesco Cavallieri