An open-label randomized controlled trial of leflunomide in patients with acute SARS-CoV-2 omicron variant infection

OBJECTIVE: To evaluate the efficacy and safety of leflunomide for the treatment of acute, symptomatic COVID-19. METHODS: A single-center, open-label, randomized controlled trial was performed during an outbreak of SARS-CoV-2 Omicron variant in December 2022. Symptomatic patients within 5 days of COVID-19 onset were randomly allocated to receive 5 days of either symptomatic treatment with leflunomide or symptomatic treatment alone. The primary endpoint was time to sustained clinical recovery. RESULTS: Fifty-seven participants were randomized into two groups: 27 received leflunomide plus symptomatic treatment and 30 were assigned to symptomatic treatment alone. Participants treated with leflunomide had a shorter fever duration [3.0 interquartile range (IQR, 2.0–4.0) days and 4.0 (IQR, 3.0–6.0) days, respectively (p = 0.027)] and reduced viral shedding [7 (IQR, 6–9.5) days and 9.0 (IQR, 7.5–12.0) days, respectively (p = 0.044)] compared with individuals treated with symptomatic treatment alone. However, there were no significant differences in time to sustained clinical recovery between the two groups [hazard ratio, 1.329 (95% confidence interval, 0.878–2.529); p = 0.207]. CONCLUSION: In acute adult COVID-19 patients presenting within 5 days of symptom onset, leflunomide combined with symptomatic treatment reduced fever duration and viral shedding time. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/about.html, ChiCTR2100051684.