Tags

Type your tag names separated by a space and hit enter

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.
Lancet. 2020 05 30; 395(10238):1695-1704.Lct

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.Department of Medicine, United Christian Hospital, Hong Kong SAR, China.Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong SAR, China.Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China.Department of Medicine, Tuen Mun Hospital, Hong Kong SAR, China.Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong SAR, China.Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, China.Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.Department of Medicine, United Christian Hospital, Hong Kong SAR, China.Department of Microbiology, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.Department of Medicine, Tuen Mun Hospital, Hong Kong SAR, China.Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, China.Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China.Department of Microbiology, Queen Elizabeth Hospital, Hong Kong SAR, China.Department of Intensive Care, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Intensive Care, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Microbiology, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.Department of Microbiology, United Christian Hospital, Hong Kong SAR, China.Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong SAR, China.Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China.Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China.Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.Department of Intensive Care, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, China.Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.Department of Microbiology, Tuen Mun Hospital, Hong Kong SAR, China.Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China. Electronic address: kyyuen@hku.hk.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32401715

Citation

Hung, Ivan Fan-Ngai, et al. "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." Lancet (London, England), vol. 395, no. 10238, 2020, pp. 1695-1704.
Hung IF, Lung KC, Tso EY, et al. 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. Lancet. 2020;395(10238):1695-1704.
Hung, I. F., Lung, K. C., Tso, E. Y., Liu, R., Chung, T. W., Chu, M. Y., Ng, Y. Y., Lo, J., Chan, J., Tam, A. R., Shum, H. P., Chan, V., Wu, A. K., Sin, K. M., Leung, W. S., Law, W. L., Lung, D. C., Sin, S., Yeung, P., ... Yuen, K. Y. (2020). 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. Lancet (London, England), 395(10238), 1695-1704. https://doi.org/10.1016/S0140-6736(20)31042-4
Hung IF, et al. 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. Lancet. 2020 05 30;395(10238):1695-1704. PubMed PMID: 32401715.
* Article titles in AMA citation format should be in sentence-case
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 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(20)31042-4 DB - PRIME DP - Unbound Medicine ER -