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)
Comparison of typical CQ dosage with high dosage CQ (600mg CQ twice daily for 10 days), showing higher mortality with high dosage, OR 2.8 [0.9 - 8.5] when controlled by age in multivariate analysis.
Increased incidence of prolonged QT and death in high dose treatment arm. Patients >75 only enrolled in high dose arm, age of high dose arm significantly higher than low dose arm (
p=0.02). Very sick at baseline, 46% in ICU, 89% on oxygen therapy (this information can be found in the preprint
[medrxiv.org]).
Borba et al., 16 Apr 2020, peer-reviewed, mean age 51.1, 28 authors.
Abstract: Original Investigation | Infectious Diseases
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
Mayla Gabriela Silva Borba, MD; Fernando Fonseca Almeida Val, PhD; Vanderson Souza Sampaio, PhD; Marcia Almeida Araújo Alexandre, MD; Gisely Cardoso Melo, PhD;
Marcelo Brito, MSc; Maria Paula Gomes Mourão, MD; José Diego Brito-Sousa, MSc; Djane Baía-da-Silva, PhD; Marcus Vinitius Farias Guerra, MD;
Ludhmila Abrahão Hajjar, MD; Rosemary Costa Pinto, BSc; Antonio Alcirley Silva Balieiro, MSc; Antônio Guilherme Fonseca Pacheco, MD;
James Dean Oliveira Santos Jr, PhD; Felipe Gomes Naveca, PhD; Mariana Simão Xavier, MSc; André Machado Siqueira, MD; Alexandre Schwarzbold, MD; Júlio Croda, MD;
Maurício Lacerda Nogueira, MD; Gustavo Adolfo Sierra Romero, MD; Quique Bassat, MD; Cor Jesus Fontes, MD; Bernardino Cláudio Albuquerque, MD;
Cláudio-Tadeu Daniel-Ribeiro, MD; Wuelton Marcelo Monteiro, PhD; Marcus Vinícius Guimarães Lacerda, MD; for the CloroCovid-19 Team
Abstract
Key Points
IMPORTANCE There is no specific antiviral therapy recommended for coronavirus disease 2019
(COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ)
requires a high concentration of the drug.
Question How safe and effective are 2
different regimens of chloroquine
diphosphate in the treatment of severe
coronavirus disease 2019 (COVID-19)?
OBJECTIVE To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.
Findings In this phase IIb randomized
clinical trial of 81 patients with COVID-19,
DESIGN, SETTING, AND PARTICIPANTS This parallel, double-masked, randomized, phase IIb
an unplanned interim analysis
clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome
recommended by an independent data
coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary
safety and monitoring board found that
care facility in Manaus, Brazilian Amazon.
a higher dosage of chloroquine
diphosphate for 10 days was associated
INTERVENTIONS Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for
with more toxic effects and lethality,
10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).
particularly affecting QTc interval
prolongation. The limited sample size
MAIN OUTCOMES AND MEASURES Primary outcome was reduction in lethality by at least 50% in
did not allow the study to show any
the high-dosage group compared with the low-dosage group. Data presented here refer primarily
benefit overall regarding treatment
to safety and lethality outcomes during treatment on day 13. Secondary end points included
efficacy.
participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be
presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4.
Meaning The preliminary findings from
the CloroCovid-19 trial suggest that
higher dosage of chloroquine should not
RESULTS Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to highdosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1
(13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4
[13.3] years) and more heart..
Late treatment
is less effective
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