High Doses of Chloroquine Should Not Be Used for Severe COVID-19 Cases

April 27, 2020
Samara Rosenfeld

Higher dosages of chloroquine can lead to safety hazards.

Mayla Gabriela Silva Borba, MD

High doses of chloroquine should not be recommended for the treatment of severe coronavirus disease 2019 (COVID-19), according to recent study findings.

The findings suggested that higher dosages for critically ill patients could lead to safety hazards, especially if taken alongside azithromycin and oseltamivir.

Mayla Gabriela Silva Borba, MD, and colleagues evaluated the safety and efficacy of 2 chloroquine dosages in patients with severe COVID-19 through a parallel, double-masked, randomized, phase 2b clinical trial with 81 patients.

Borba, from Amazonas State University in Brazil, and the team of investigators included patients hospitalized with clinical suspicion of COVID-19. Patients were >18 years old with a respiratory rate >24 rpm, heart rate >125 bpm, peripheral oxygen saturation <90% in ambient air, and/or shock.

Each patient received either high-dosage chloroquine (600 mg twice daily for 10 days) or low-dosage (450 mg twice daily on day 1 and once daily for 4 days). Placebos were also used in the lower dose group to standardize treatment.

The primary outcome was reduction in lethality by >50% in the high-dosage group compared to the lower dosage. Additional measures included participant clinical status, laboratory examinations, and electrocardiogram results.

Overall, 40 patients were randomized to the low-dosage group and 41 to the high-dosage group. A majority of patients (76.5%) had COVID-19 confirmed by a reverse transcription-polymerase chain reaction. Those with unconfirmed cases had clinical and epidemiological presentation compatible with COVID-19.

Patients were a mean age of 51.1 years old and predominantly men (75.3%). Hypertension (45.5%), alcohol use disorder (27.5%), and diabetes (25.5%) were the most frequent comorbidities. Older men with a mean age of 54.7 years old versus 47.4 years old with more heart disease (17.9% vs 0) were in the high-dosage group.

The overall lethality rate was 27.2% (95% CI, 17.9-38.2). Lethality until day 13 of the study was 39% in the high-dosage group and 15% in the low-dosage group. The high-dosage group was associated with lethality (OR, 3.6; 95% CI, 1.2-10.6).

The high-dosage group had more instances of QTc interval >500 milliseconds (18.9% vs 11.1% in the low-dosage group).

Among 5 patients with chronic cardiac disease, 3 (60%) died.

The COVID-19 pandemic has forced healthcare providers to choose between offering medical assistance and generating and reporting reliable data. But global recommendations were being made based on unpowered studies and drugs are being prescribed in a compassionate manner, the study authors wrote.

Although chloroquine was a safe drug used to treat malaria, for patients with COVID-19, the team’s study raised enough red flags to stop the use of a high-dosage regimen (12 g of chloroquine for 10 days) due to the risks of toxic effects overcoming the benefits. Chloroquine could be used to help patients improve and to decrease the viral load in respiratory secretions, but the investigators’ data did not provide such evidence.

The investigators plan to continue to enroll patients in the low-dosage group to complete the original planned sample size of the study.

The study, “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,” was published online in JAMA Network Open.