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
Copyright © 2020 Elsevier Ltd. All rights reserved..
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.
| Errataetall: |
CommentIn: Lancet. 2020 May 30;395(10238):1670-1671. - PMID 32401712 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:395 |
|---|---|
| Enthalten in: |
Lancet (London, England) - 395(2020), 10238 vom: 30. Mai, Seite 1695-1704 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.06.2020 Date Revised 07.12.2022 published: Print-Electronic ClinicalTrials.gov: NCT04276688 CommentIn: Lancet. 2020 May 30;395(10238):1670-1671. - PMID 32401712 Citation Status MEDLINE |
|---|
| doi: |
10.1016/S0140-6736(20)31042-4 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM309846935 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM309846935 | ||
| 003 | DE-627 | ||
| 005 | 20231225134815.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/S0140-6736(20)31042-4 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1032.xml |
| 035 | |a (DE-627)NLM309846935 | ||
| 035 | |a (NLM)32401715 | ||
| 035 | |a (PII)S0140-6736(20)31042-4 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hung, Ivan Fan-Ngai |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19 |b an open-label, randomised, phase 2 trial |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.06.2020 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04276688 | ||
| 500 | |a CommentIn: Lancet. 2020 May 30;395(10238):1670-1671. - PMID 32401712 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a lopinavir-ritonavir drug combination |2 NLM | |
| 650 | 7 | |a Interferon beta-1b |2 NLM | |
| 650 | 7 | |a 145155-23-3 |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 650 | 7 | |a Ribavirin |2 NLM | |
| 650 | 7 | |a 49717AWG6K |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Lung, Kwok-Cheung |e verfasserin |4 aut | |
| 700 | 1 | |a Tso, Eugene Yuk-Keung |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Raymond |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Tom Wai-Hin |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Man-Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Yuk-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Lo, Jenny |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jacky |e verfasserin |4 aut | |
| 700 | 1 | |a Tam, Anthony Raymond |e verfasserin |4 aut | |
| 700 | 1 | |a Shum, Hoi-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Veronica |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Alan Ka-Lun |e verfasserin |4 aut | |
| 700 | 1 | |a Sin, Kit-Man |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Wai-Shing |e verfasserin |4 aut | |
| 700 | 1 | |a Law, Wai-Lam |e verfasserin |4 aut | |
| 700 | 1 | |a Lung, David Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Sin, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Yeung, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Yip, Cyril Chik-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ricky Ruiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Fung, Agnes Yim-Fong |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Erica Yuen-Wing |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Kit-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Ip, Jonathan Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Allen Wing-Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Wan-Mui |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Anthony Chin-Ki |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Rodney |e verfasserin |4 aut | |
| 700 | 1 | |a Fung, Kitty |e verfasserin |4 aut | |
| 700 | 1 | |a Yeung, Alwin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Tak-Chiu |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Johnny Wai-Man |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Wing-Wah |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Wai-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jasper Fuk-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Lie, Albert Kwok-Wai |e verfasserin |4 aut | |
| 700 | 1 | |a Tsang, Owen Tak-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Vincent Chi-Chung |e verfasserin |4 aut | |
| 700 | 1 | |a Que, Tak-Lun |e verfasserin |4 aut | |
| 700 | 1 | |a Lau, Chak-Sing |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Kwok-Hung |e verfasserin |4 aut | |
| 700 | 1 | |a To, Kelvin Kai-Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Lancet (London, England) |d 1945 |g 395(2020), 10238 vom: 30. Mai, Seite 1695-1704 |w (DE-627)NLM000473936 |x 1474-547X |7 nnns |
| 773 | 1 | 8 | |g volume:395 |g year:2020 |g number:10238 |g day:30 |g month:05 |g pages:1695-1704 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/S0140-6736(20)31042-4 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 395 |j 2020 |e 10238 |b 30 |c 05 |h 1695-1704 | ||