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.
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Hung Ivan Fan-Ngai, Lung Kwok-Cheung, Tso Eugene Yuk-Keung, Liu Raymond, Chung Tom Wai-Hin, Chu Man-Yee, Ng Yuk-Yung, Lo Jenny, Chan Jacky, Tam Anthony Raymond, Shum Hoi-Ping, Chan Veronica, Wu Alan Ka-Lun, Sin Kit-Man, Leung Wai-Shing, Law Wai-Lam, Lung David Christopher, Sin Simon, Yeung Pauline, Yip Cyril Chik-Yan, Zhang Ricky Ruiqi, Fung Agnes Yim-Fong, Yan Erica Yuen-Wing, Leung Kit-Hang, Ip Jonathan Daniel, Chu Allen Wing-Ho, Chan Wan-Mui, Ng Anthony Chin-Ki, Lee Rodney, Fung Kitty, Yeung Alwin, Wu Tak-Chiu, Chan Johnny Wai-Man, Yan Wing-Wah, Chan Wai-Ming, Chan Jasper Fuk-Woo, Lie Albert Kwok-Wai, Tsang Owen Tak-Yin, Cheng Vincent Chi-Chung, Que Tak-Lun, Lau Chak-Sing, Chan Kwok-Hung, To Kelvin Kai-Wang, Yuen Kwok-Yung
Аннотация
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.