tetano
Editor, Senior Moderator
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.
**** IF[SUP]1[/SUP], Lung KC[SUP]2[/SUP], Tso EY[SUP]3[/SUP], Liu R[SUP]4[/SUP], Chung TW[SUP]5[/SUP], Chu MY[SUP]6[/SUP], Ng YY[SUP]7[/SUP], Lo J[SUP]4[/SUP], Chan J[SUP]8[/SUP], Tam AR[SUP]9[/SUP], Shum HP[SUP]10[/SUP], Chan V[SUP]3[/SUP], Wu AK[SUP]11[/SUP], Sin KM[SUP]7[/SUP], Leung WS[SUP]8[/SUP], Law WL[SUP]6[/SUP], Lung DC[SUP]12[/SUP], Sin S[SUP]13[/SUP], Yeung P[SUP]13[/SUP], Yip CC[SUP]5[/SUP], Zhang RR[SUP]1[/SUP], Fung AY[SUP]14[/SUP], Yan EY[SUP]14[/SUP], Leung KH[SUP]14[/SUP], Ip JD[SUP]14[/SUP], Chu AW[SUP]14[/SUP], Chan WM[SUP]14[/SUP], Ng AC[SUP]14[/SUP], Lee R[SUP]11[/SUP], Fung K[SUP]15[/SUP], Yeung A[SUP]4[/SUP], Wu TC[SUP]6[/SUP], Chan JW[SUP]6[/SUP], Yan WW[SUP]10[/SUP], Chan WM[SUP]13[/SUP], Chan JF[SUP]14[/SUP], Lie AK[SUP]9[/SUP], Tsang OT[SUP]8[/SUP], Cheng VC[SUP]5[/SUP], Que TL[SUP]16[/SUP], Lau CS[SUP]9[/SUP], Chan KH[SUP]14[/SUP], To KK[SUP]14[/SUP], Yuen KY[SUP]17[/SUP].
Author information
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
Free PMC Article
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.
**** IF[SUP]1[/SUP], Lung KC[SUP]2[/SUP], Tso EY[SUP]3[/SUP], Liu R[SUP]4[/SUP], Chung TW[SUP]5[/SUP], Chu MY[SUP]6[/SUP], Ng YY[SUP]7[/SUP], Lo J[SUP]4[/SUP], Chan J[SUP]8[/SUP], Tam AR[SUP]9[/SUP], Shum HP[SUP]10[/SUP], Chan V[SUP]3[/SUP], Wu AK[SUP]11[/SUP], Sin KM[SUP]7[/SUP], Leung WS[SUP]8[/SUP], Law WL[SUP]6[/SUP], Lung DC[SUP]12[/SUP], Sin S[SUP]13[/SUP], Yeung P[SUP]13[/SUP], Yip CC[SUP]5[/SUP], Zhang RR[SUP]1[/SUP], Fung AY[SUP]14[/SUP], Yan EY[SUP]14[/SUP], Leung KH[SUP]14[/SUP], Ip JD[SUP]14[/SUP], Chu AW[SUP]14[/SUP], Chan WM[SUP]14[/SUP], Ng AC[SUP]14[/SUP], Lee R[SUP]11[/SUP], Fung K[SUP]15[/SUP], Yeung A[SUP]4[/SUP], Wu TC[SUP]6[/SUP], Chan JW[SUP]6[/SUP], Yan WW[SUP]10[/SUP], Chan WM[SUP]13[/SUP], Chan JF[SUP]14[/SUP], Lie AK[SUP]9[/SUP], Tsang OT[SUP]8[/SUP], Cheng VC[SUP]5[/SUP], Que TL[SUP]16[/SUP], Lau CS[SUP]9[/SUP], Chan KH[SUP]14[/SUP], To KK[SUP]14[/SUP], Yuen KY[SUP]17[/SUP].
Author information
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
Free PMC Article