干扰素 beta-1b、洛匹那韦利托那韦和利巴韦林三联治疗住院 COVID-19 患者：一项开放标签、随机、2 期试验。
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.
机构信息
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.
出版信息
Lancet. 2020 May 30;395(10238):1695-1704. doi: 10.1016/S0140-6736(20)31042-4. Epub 2020 May 10.
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.
背景
有效的抗病毒治疗对于应对 2019 年冠状病毒病（COVID-19）大流行非常重要。我们评估了联合使用干扰素 beta-1b、洛匹那韦/利托那韦和利巴韦林治疗 COVID-19 患者的疗效和安全性。
方法
这是一项在香港六家医院住院的 COVID-19 成年患者中进行的多中心、前瞻性、开放性标签、随机、2 期试验。患者按 2:1 随机分配接受 14 天的洛匹那韦 400 mg 和利托那韦 100 mg 每 12 小时一次、利巴韦林 400 mg 每 12 小时一次和三剂 800 万国际单位干扰素 beta-1b 隔日（联合组）或 14 天的洛匹那韦 400 mg 和利托那韦 100 mg 每 12 小时一次（对照组）。主要终点是从开始鼻咽拭子检测到严重急性呼吸综合征冠状病毒 2 RT-PCR 阴性的时间，并在意向治疗人群中进行。该研究在 ClinicalTrials.gov 注册，NCT04276688。
结果
2020 年 2 月 10 日至 3 月 20 日期间，共招募了 127 名患者；86 名患者被随机分配到联合组，41 名患者被分配到对照组。从症状出现到开始研究治疗的中位时间为 5 天（IQR 3-7）。与对照组相比，联合组从开始研究治疗到鼻咽拭子转阴的中位时间明显更短（7 天[IQR 5-11] vs. 12 天[8-15]；危险比 4.37[95%CI 1.86-10.24]，p=0.0010）。不良反应包括自限性恶心和腹泻，两组间无差异。对照组有 1 名患者因生化性肝炎停止使用洛匹那韦-利托那韦。在研究期间没有患者死亡。
解释
早期三联抗病毒治疗在缓解症状、缩短病毒脱落和住院时间方面优于洛匹那韦-利托那韦单独治疗，对轻度至中度 COVID-19 患者安全。有必要对以干扰素 beta-1b 为骨干的双联抗病毒治疗进行进一步的临床研究。
资金
邵氏基金会、Richard 和 Carol Yu、May Tam Mak Mei Yin 和三明明德项目。
Zotero 插件