ABSTRACT
Background: The outbreak of novel coronavirus pneumonia is very serious, and no effective antiviral treatment has been confirmed. The fresh drug research and development cycle is too long to meet clinical emergency needs, and "old drugs and brand new applications" have a huge therapeutic potential. During our previous treatment, we found that the lopinavir/ritonavir treatment recommended in the Fifth edition of the treatment plan had little effect. Earlier studies have shown that chloroquine can inhibit coronavirus replication through multiple mechanisms. Our previous use of chloroquine to treat patients with SARS-CoV-2(novel coronavirus)-infected pneumonia has a higher negative rate of nucleic acid in throat swabs within 5 days after administration than that using lopinavir/ritonavir. However, the half-life and side effects of chloroquine vary greatly among individuals. Methods/design We plan to conduct a prospective, open-label, multicenter randomized controlled, comprehensive treatment clinical study. The study consisted of three phases: a screening period of 1-110 days, a treatment period of no more than 28 days, and a follow-up period of 1 month. Participants will be assessed at baseline and on days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 21, and 28 after the intervention begins. In this study, chloroquine and lopinavir/ritonavir tablets were used to treat patients with eligible novel coronavirus pneumonia diagnosed at various centers between February 12, 2020 and May 31, 2020. The efficacy and safety of chloroquine and lopinavir/ritonavir are to be evaluated. At the same time, explore the correlation between patient genetic polymorphisms and chloroquine steady-state concentration, therapeutic effects and adverse reactions in the body. It is an anti-virus for pneumonitis caused by novel coronavirus. The optimization and update of the antiviral treatment plan provides evidence-based evidence. Disscussion Our study is a prospective, open-label, multicenter randomized controlled, comprehensive treatment clinical study to evaluate the efficacy and safety of chloroquine phosphate and lopinavir/ritonavir in patients with mild/general COVID-2019. The results of this study will provide valuable clinical evidence for the treatment of novel coronavirus pneumonia.
Subject(s)
COVID-19 , Coronavirus Infections , PneumoniaABSTRACT
Background Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. Method In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. Results A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Conclusions Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.