Litwin Alain H, Lum Paula J, Taylor Lynn E, Mehta Shruti H, Tsui Judith I, Feinberg Judith, Kim Arthur Y, Norton Brianna L, Heo Moonseong, Arnsten Julia, Meissner Paul, Karasz Alison, Mckee M Diane, Ward John W, Johnson Nirah, Pericot-Valverde Irene, Agyemang Linda, Stein Ellen S, Thomas Aurielle, Borsuk Courtney, Blalock Kendra L, Wilkinson Samuel, Wagner Katherine, Roche Jillian, Murray-Krezan Cristina, Anderson Jessica, Jacobsohn Vanessa, Luetkemeyer Anne F, Falade-Nwulia Oluwaseun, Page Kimberly
School of Health Research, Clemson University, Clemson, SC, USA; Department of Medicine, University of South Carolina School of Medicine, Greenville, SC, USA; Department of Medicine, Prisma Health, Greenville, SC, USA.
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Lancet Gastroenterol Hepatol. 2022 Dec;7(12):1112-1127. doi: 10.1016/S2468-1253(22)00275-8.
To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use.
We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640.
Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group).
In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support.
Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.
为实现世界卫生组织消除丙型肝炎病毒（HCV）这一公共威胁的目标，迫切需要提高注射吸毒者（PWID）中HCV治疗的接受率。尚未确定针对PWID的最佳HCV联合治疗模式。我们旨在比较两种以患者为中心的针对仍在吸毒的PWID的HCV护理模式。
我们在美国八个城市的八个阿片类药物治疗项目和15个社区卫生中心进行了一项实用随机对照试验。在研究入组90天内仍在积极注射毒品的PWID被随机分配（1:1）至患者导航组或改良直接观察疗法（mDOT）组，采用计算机生成的2至6的可变区组大小，并按城市、临床环境和肝硬化状态进行分层。除数据协调中心的一名授权数据管理员外，随机化编码在一个集中式REDCap数据库平台中对所有研究者和研究人员保密。所有参与者均口服固定剂量复方片剂（索磷布韦400mg加维帕他韦100mg），每日一次，共12周。主要结局为持续病毒学应答（SVR；在治疗结束后70天至365天之间通过病历审查确定，若无法获取，则通过研究采血确定），次要结局为治疗开始、依从性（通过电子泡罩包装测量）和治疗完成情况。分析在改良意向性治疗（mITT；所有开始治疗的患者）、意向性治疗（所有随机分组的患者）和符合方案人群中进行。本试验已在ClinicalTrials.gov注册，注册号为NCT02824640。
2016年9月15日至2018年8月14日期间，共筛查了1891人，排除1136人（213人拒绝参与，923人不符合入选标准）。我们将755名参与者随机分配至患者导航组（n = 379）或mDOT组（n = 376）。在随机分组并开始治疗的参与者的mITT样本（n = 623）中，mDOT组306名参与者中有226名（74% [95%CI 69 - 79]）达到SVR，患者导航组317名参与者中有236名（76% [69 - 79]）达到SVR，两组之间无显著差异（调整优势比[AOR] 0·97 [95%CI 0·66 - 1·42]；p = 0·35）。在意向性治疗样本（n = 755）中，mDOT组376名参与者中有226名（60% [95%CI 55 - 65]）达到SVR，患者导航组379名参与者中有236名（62% [57 - 67]）达到SVR（AOR 0·92 [0·68 - 1·25]；p = 0·61），在符合方案样本（n = 501）中，mDOT组248名参与者中有226名（91% [87 - 94]）达到SVR，患者导航组253名参与者中有235名（93% [89 - 96]）达到SVR（AOR 0·79 [0·41 - 1·55]；p = 0·44）。mDOT组376名参与者中有306名（81%）开始治疗，患者导航组379名参与者中有317名（84%）开始治疗（AOR 0·86 [0·58 - 1·26]；p = 0·44），其中，mDOT组251名（82%）参与者和患者导航组264名（83%）参与者完成治疗（AOR 0·90 [0·58 - 1·39]；p = 0·63）。mDOT组的平均每日依从性高于患者导航组（78% [95%CI 75 - 81]）对（73% [70 - 77]），差异为4·7%（[1·9 - 7·4]；p = 0·0010）。共报告了421例严重不良事件（mDOT组217例，患者导航组204例），最常见的是住院（mDOT组176例对患者导航组161例）。
在这项针对仍在吸毒的PWID的试验中，两种模式均导致高SVR。尽管mDOT组的依从性显著高于患者导航组，但两组之间的SVR无显著差异。依从性和治疗完成率的提高与SVR可能性增加相关。这些结果表明，在mDOT或患者导航支持下，仍在吸毒的PWID在不同环境中均可实现高SVR。
以患者为中心的结果研究机构、吉利德科学公司、奎斯特诊断公司、Monogram生物科学公司和奥瑞Sure技术公司。
