TY - JOUR
T1 - Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19
T2 - 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
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/5/30
Y1 - 2020/5/30
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.
AB - 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.
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U2 - 10.1016/S0140-6736(20)31042-4
DO - 10.1016/S0140-6736(20)31042-4
M3 - Article
C2 - 32401715
AN - SCOPUS:85085317504
SN - 0140-6736
VL - 395
SP - 1695
EP - 1704
JO - The Lancet
JF - The Lancet
IS - 10238
ER -