Safety and Efficacy of Oral administrated Cepharanthine in Non-hospitalized, asymptomatic or mild COVID-19 patients: A Double-blind, Randomized, Placebo-controlled Trial

Abstract

AbstractCepharanthine (CEP) is a natural remedy that potently inhibits SARS-CoV-2 activity both in vitro and in vivo. We conducted a proof-of-concept, double-blind, randomized, placebo-controlled trial among adults with asymptomatic or mild coronavirus disease 2019 (COVID-19). Patients were stratified randomly to de novo infection or viral rebound, and assigned in a 1:1:1 ratio to receive 60 mg/day or 120 mg/day of CEP or placebo. Primary outcome the time from randomization to negative nasopharyngeal swab, and safety were evaluated. A total of 262 de novo infected and 124 viral rebound patients underwent randomization. In the 188 de novo patients included in modified intention-to-treat (mITT) population, when compared with placebo, 60 mg/day CEP slightly shortened the time to negative (difference=-0.77 days, hazard ratio (HR)=1.40, 95% CI 0.97 to 2.01, p=0.072), and 120 mg/day CEP did not show the trend. Among de novo patients in the per-protocol set (PPS), 60 mg/day CEP significantly shortened the time to negative (difference=-0.87 days, HR=1.56, 95% CI 1.03 to 2.37, p=0.035). Among viral rebound patients in the mITT population, neither 120 mg/day nor 60 mg/day CEP significantly shortened the time to negative compared to placebo. Adverse events were not different among the three groups, and no serious adverse events occurred. Treatment of asymptomatic or mild Covid-19 with 120 mg/day or 60 mg/day CEP did not shorten the time to negative compared with placebo, without evident safety concerns. Among de novo infected patients with good compliance, 60 mg/day CEP significantly shortened the time to negative compared with placebo (NCT05398705).