A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial.
A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial.
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DOI：
10.1016/s2468-1253(21)00397-6
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发表时间：
2022-04
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影响因子：
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通讯作者：
Sulkowski M
中科院分区：
文献类型：
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作者：
Solomon SS;Wagner-Cardoso S;Smeaton L;Sowah LA;Wimbish C;Robbins G;Brates I;Scello C;Son A;Avihingsanon A;Linas B;Anthony D;Nunes EP;Kliemann DA;Supparatpinyo K;Kityo C;Tebas P;Bennet JA;Santana-Bagur J;Benson CA;Van Schalkwyk M;Cheinquer N;Naggie S;Wyles D;Sulkowski M
尽管包括通用配方在内的直接抗病毒药物广泛可用，但在全球采用丙型肝炎病毒（HCV）治疗方面取得的进展有限。扩大治疗的障碍包括诊断和监测测试的可得性和可及性、卫生保健基础设施以及治疗期间频繁访问的要求。ACTG A5360是一项4期、开放标签、单臂试验，在巴西、南非、泰国、乌干达和美国的38个地点进行。主要纳入标准为年龄18岁或以上、有活动性HCV感染证据（HCV RNA >1000 IU/mL）和未接受HCV治疗；伴有代偿性肝硬化和HIV/HCV合并感染的患者也被纳入研究，但他们的入组是有限制的。所有参与者接受固定剂量的口服索非布韦（400毫克）和维帕他韦（100毫克），每天一次，持续12周。最小监测（MINMON）方法由四个部分组成：(1)治疗前不进行基因分型；(2)整个疗程（84片）在入院时配药；(3)没有预约就诊或实验室监测；(4)在依从性第4周和第22周有两个远程联络点，安排在第24周（- 2周至+4周）进行结果评估。错过第24周窗口期的参与者可以在第72周之前的任何时间再次访问以评估治疗反应。在第24周访问之前，任何理由的计划外访问都是允许的。主要疗效终点是持续病毒学应答（SVR），定义为HCV RNA低于治疗开始后至少22周测量的定量下限；主要安全性指标为严重不良事件。主要疗效分析包括所有开始治疗的参与者，采用缺失=失败的方法。主要的安全性分析包括所有开始治疗并至少进行一次治疗后评估的参与者。该试验已在ClinicalTrials.gov注册，编号NCT03512210。在2018年10月22日至2019年7月19日期间，在所有38个站点招募了400名参与者；399人开始接受治疗。在SVR评估访问中，397名参与者中有355名（89%）报告在12周的治疗期间服用了100%的试验药物；两名患者在入组后没有进行任何随访，因此被排除在安全性分析之外。总体而言，399例开始治疗的患者中有379例SVR （95.0%, 95% CI 92.4 - 96.7）。397名参与者中有14名（4%）在治疗开始至第28周期间报告了严重不良事件；没有一例与治疗相关或导致治疗中断或死亡。399名参与者中有15名（4%）有计划外的访问；没有一个与治疗有关。在这种多样化的全球HCV人群中，MINMON方法与索非布韦-维帕他韦治疗是安全的，并且实现了与现实世界数据中观察到的标准监测相当的SVR。再加上创新的病例发现战略，这一战略可能对全球消除丙型肝炎病毒议程至关重要。美国国立卫生研究院和吉利德科学研究所。
Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (−2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4–96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. In this diverse global population of people with HCV, the MINMON approach with sofosbuvir–velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. US National Institutes of Health and Gilead Sciences.