Efficacy of Levamisole with Standard Care Treatment vs Standard Care in Clinical Presentations of Non-Hospitalized Patients with COVID-19: A Randomized Clinical Trial

Introduction: Levamisole (LVM) demonstrated clinical benefit in a trial in patients with mild to moderate coronavirus disease 2019 (COVID-19), but its effect in a larger sample size needs to be confirmed. Methods In this randomized open-label trial, we enrolled non-hospitalized patients with mild to moderate COVID-19 at nine health centers in Tehran province, Iran, in 2021. Patients were randomly assigned to receive a 10-day course of LVM with standard care (n = 185), or standard care (n = 180) in a 1:1 ratio. On days 1 to 10, LVM was administered orally at a dosage of 50 mg. The participants were called and followed on days 1, 3, 5, 7, 9, and 14. The outcomes were general health condition, hospitalization rate, sign and symptoms, and adverse events (AEs). Generalized Estimating Equations model was used for analysis. Results Among 507 randomized patients, 473 started the experiment and received LVM in addition to standard care or received only the standard care (median age, 40 [IQR, 32-50.75] years; 164 [44.9%] women; 9.4% had diabetes, 8.8% hypertension, 1.6% cardiovascular disease), and 346 (98%) completed the trial. Compared to control group, LVM decreased the general health condition of the patients (B=-0.635; CI= -0.041, -0.329; P= 0.000). Patients in the LVM with standard care group had significantly lower odds of developing fever (OR= 0.260; 95% CI= ‎0.11‎‎3‎-0.59‎‎9‎; P = .002), chills (OR= 0.223; 95% CI= ‎‎0.07‎‎6‎-‎0.64‎‎8‎; P = 0.006), fatigue (OR= 0.576; 95% CI= ‎0.34‎‎6‎-‎0.96‎‎0‎‎; P = ‎0.034), and myalgia (OR= 0.54‎‎4‎; 95% CI= ‎0.31‎‎7‎-‎0.93‎‎2‎‎; P =0.027). During the therapy, there was no significant difference in the parameters of dyspnea, cough, diarrhea, nausea, vomiting, sore throat, hyposmia, dysgeusia, and anorexia (P > 0.05). No significant difference was observed in the rate of hospitalization. Although the intervention group had greater AEs than the control group, yet, the difference was not statistically significant. Conclusions LVM has clinical benefit in improving health condition of patients with mild to moderate COVID-19. Further studies are needed to confirm our findings. Trial Registration: Iranian Registry of Clinical Trials: IRCT20201124049480N1; Registration date: 28/03/2021.