TY - JOUR T1 - Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. AU - Hung,Ivan Fan-Ngai, AU - Lung,Kwok-Cheung, AU - Tso,Eugene Yuk-Keung, AU - Liu,Raymond, AU - Chung,Tom Wai-Hin, AU - Chu,Man-Yee, AU - Ng,Yuk-Yung, AU - Lo,Jenny, AU - Chan,Jacky, AU - Tam,Anthony Raymond, AU - Shum,Hoi-Ping, AU - Chan,Veronica, AU - Wu,Alan Ka-Lun, AU - Sin,Kit-Man, AU - Leung,Wai-Shing, AU - Law,Wai-Lam, AU - Lung,David Christopher, AU - Sin,Simon, AU - Yeung,Pauline, AU - Yip,Cyril Chik-Yan, AU - Zhang,Ricky Ruiqi, AU - Fung,Agnes Yim-Fong, AU - Yan,Erica Yuen-Wing, AU - Leung,Kit-Hang, AU - Ip,Jonathan Daniel, AU - Chu,Allen Wing-Ho, AU - Chan,Wan-Mui, AU - Ng,Anthony Chin-Ki, AU - Lee,Rodney, AU - Fung,Kitty, AU - Yeung,Alwin, AU - Wu,Tak-Chiu, AU - Chan,Johnny Wai-Man, AU - Yan,Wing-Wah, AU - Chan,Wai-Ming, AU - Chan,Jasper Fuk-Woo, AU - Lie,Albert Kwok-Wai, AU - Tsang,Owen Tak-Yin, AU - Cheng,Vincent Chi-Chung, AU - Que,Tak-Lun, AU - Lau,Chak-Sing, AU - Chan,Kwok-Hung, AU - To,Kelvin Kai-Wang, AU - Yuen,Kwok-Yung, Y1 - 2020/05/10/ PY - 2020/04/03/received PY - 2020/04/21/revised PY - 2020/04/23/accepted PY - 2020/5/14/pubmed PY - 2020/6/3/medline PY - 2020/5/14/entrez SP - 1695 EP - 1704 JF - Lancet (London, England) JO - Lancet VL - 395 IS - 10238 N2 - BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/32401715/full_citation DB - PRIME DP - Unbound Medicine ER -