Lancet. 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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Lancet. 2020 May 8. pii: S0140-6736(20)31042-4. doi: 10.1016/S0140-6736(20)31042-4. [Epub ahead of print]
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.


**** IF¹, Lung KC², Tso EY³, Liu R⁴, Chung TW⁵, Chu MY⁶, Ng YY⁷, Lo J⁴, Chan J⁸, Tam AR⁹, Shum HP¹⁰, Chan V³, Wu AK¹¹, Sin KM⁷, Leung WS⁸, Law WL⁶, Lung DC¹², Sin S¹³, Yeung P¹³, Yip CC⁵, Zhang RR¹, Fung AY¹⁴, Yan EY¹⁴, Leung KH¹⁴, Ip JD¹⁴, Chu AW¹⁴, Chan WM¹⁴, Ng AC¹⁴, Lee R¹¹, Fung K¹⁵, Yeung A⁴, Wu TC⁶, Chan JW⁶, Yan WW¹⁰, Chan WM¹³, Chan JF¹⁴, Lie AK⁹, Tsang OT⁸, Cheng VC⁵, Que TL¹⁶, Lau CS⁹, Chan KH¹⁴, To KK¹⁴, Yuen KY¹⁷.

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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.
Copyright ? 2020 Elsevier Ltd. All rights reserved.



PMID:32401715DOI:10.1016/S0140-6736(20)31042-4
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