2. Academic Validation
  3. 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

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 May 30;395(10238):1695-1704. doi: 10.1016/S0140-6736(20)31042-4.
Ivan Fan-Ngai Hung 1,  Kwok-Cheung Lung 2,  Eugene Yuk-Keung Tso 3,  Raymond Liu 4,  Tom Wai-Hin Chung 5,  Man-Yee Chu 6,  Yuk-Yung Ng 7,  Jenny Lo 4,  Jacky Chan 8,  Anthony Raymond Tam 9,  Hoi-Ping Shum 10,  Veronica Chan 3,  Alan Ka-Lun Wu 11,  Kit-Man Sin 7,  Wai-Shing Leung 8,  Wai-Lam Law 6,  David Christopher Lung 12,  Simon Sin 13,  Pauline Yeung 13,  Cyril Chik-Yan Yip 5,  Ricky Ruiqi Zhang 1,  Agnes Yim-Fong Fung 14,  Erica Yuen-Wing Yan 14,  Kit-Hang Leung 14,  Jonathan Daniel Ip 14,  Allen Wing-Ho Chu 14,  Wan-Mui Chan 14,  Anthony Chin-Ki Ng 14,  Rodney Lee 11,  Kitty Fung 15,  Alwin Yeung 4,  Tak-Chiu Wu 6,  Johnny Wai-Man Chan 6,  Wing-Wah Yan 10,  Wai-Ming Chan 13,  Jasper Fuk-Woo Chan 14,  Albert Kwok-Wai Lie 9,  Owen Tak-Yin Tsang 8,  Vincent Chi-Chung Cheng 5,  Tak-Lun Que 16,  Chak-Sing Lau 9,  Kwok-Hung Chan 14,  Kelvin Kai-Wang To 14,  Kwok-Yung Yuen 17
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.
  • 3 Department of Medicine, United Christian Hospital, Hong Kong SAR, China.
  • 4 Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong SAR, China.
  • 5 Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.
  • 6 Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China.
  • 7 Department of Medicine, Tuen Mun Hospital, Hong Kong SAR, China.
  • 8 Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, China.
  • 9 Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.
  • 10 Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.
  • 11 Department of Microbiology, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.
  • 12 Department of Microbiology, Queen Elizabeth Hospital, Hong Kong SAR, China.
  • 13 Department of Intensive Care, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.
  • 14 State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.
  • 15 Department of Microbiology, United Christian Hospital, Hong Kong SAR, China.
  • 16 Department of Microbiology, Tuen Mun Hospital, Hong Kong SAR, China.
  • 17 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.
PMID: 32401715 DOI: 10.1016/S0140-6736(20)31042-4
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.

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