The Efficacy and Safety of Adding Chlorpromazine to Atazanavir/Ritonavir Regimen in the Treatment of Moderate COVID-19 Patients, a Randomized Double-blind Clinical Trial
Authors:   Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran., Ramezaninejad Sima , Namvar Hamid Reza ,   Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran., Sohrabi Masoumeh ,   Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran., Darvishnia David ,   Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran., Ahangar Nematollah ,   Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran., Alikhani Ahmad ,   Department of Infectious Diseases, Antimicrobial Resistance Research Center, Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran., Abbaspour Hamideh ,   Department of Clinical of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran., Valadan Reza ,   Department of Immunology, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran., Akbari Zahra ,   Department of Infectious Diseases, Antimicrobial Resistance Research Center, Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran., Akbari Jafar ,   Department of Clinical of Pharmaceutics, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran., Ghasemian Roya ,   Department of Infectious Diseases, Antimicrobial Resistance Research Center, Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran., Salehifar Ebrahim ,   Department of Clinical of Pharmaceutics, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Published: September 2023

Background: According to COVID-19 mutation and no defined treatment, it is necessary to find effective treatment. Chlorpromazine, a phenothiazine antipsychotic drug, has been shown in animal studies to have antiviral effects by inhibiting clathrin-mediated endocytosis. The aim of this study was to evaluate the effectiveness of adding chlorpromazine to the atazanavir/ritonavir regimen in the treatment of moderate COVID-19 patients. Methods: In this randomized double-blind clinical trial, sixty hospitalized patients with moderate COVID-19 confirmed by CT findings or polymerase chain reaction (PCR) were enrolled. All patients received atazanavir/ritonavir 300mg/100mg once daily. In two parallel groups, chlorpromazine 25 mg three times a day or a placebo was administered for up to 14 days. Complete blood count with differential, C-reactive protein (CRP), liver enzymes, and erythrocyte sedimentation rate was measured on days 1, 3, 5, 7, and 10. The primary outcome was the improvement of oxygen saturation and the secondary outcome was the duration of hospitalization and conversion of PCR test results. Results: Oxygen saturation during the hospitalization was not different among the two groups. The mean duration of hospitalization in the chlorpromazine group was 7.4±2.7 days and in the placebo was 8.2±3 days (P=0.2). Compared to baseline, both groups showed an increase in white blood cell count (P=0.04) and polymorphonuclear cells (P=0.04) but lymphocyte count decreased. At the end of the study, the PCR test was negative in 100% of patients in the chlorpromazine group and 95% of patients in the placebo group. Conclusion: In adult hospitalized patients with moderate symptomatic COVID-19, adding chlorpromazine to the atazanavir/ritonavir regimen did not improve outcomes.