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

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.