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

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  • Mayla Borba, MD
  • Fernando Val, PhD
  • Vanderson Sampaio, PhD
  • ...
  • Guimaraes Lacerda, MD
Journal JAMA Network
Date April 24, 2020

Randomized, double blind clinical trial of 81 patients in Brazil comparing different dosages of chloroquine (1200 mg daily vs 450 mg daily) in the treatment of COVID-19. Study found increased incidence of prolonged QT and lethality in the high dose treatment arm.

This study had a predefined sample size of 440 patients, but the study was discontinued after enrollment of only 81 patients (41 to high-dose group and 40 to low-dose group) when lethality in the high dose group far exceeded that in the low-dose group (39.0% vs 15.0%).

The study researchers are currently under investigation for treating patients in the high-dose group with chloroquine 1200mg daily, which likely resulted in drug overdoses and a high fatality rate.

Major Issues

At the time of this study, it was still unclear if there was therapeutic benefit to chloroquine in treatment of COVID-19. There were very few randomized controlled trials of this therapy by this time. Thus, it was odd that the researchers decide to compare two different treatment doses of chloroquine as opposed to chloroquine vs standard therapy. This study has been further criticized for the high cumulative doses of chloroquine prescribed to patients. To date, there are no medical guidelines that recommend 12g of chloroquine over a 10-day period, and many guidelines suggest toxicity well below these doses.

The study researchers are now under investigation for prescribing these high doses which may have resulted in unnecessary deaths.

Minor Issues

No minor issues identified at this time.


This study demonstrated that chloroquine taken in doses over 1000mg daily for multiple days can be lethal in critically ill patients.

Article Revisions

None at this time.