Center for Tuberculosis and Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.
Uganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda.
PLoS Med. 2021 May 6;18(5):e1003628. doi: 10.1371/journal.pmed.1003628. eCollection 2021 May.
Adherence to and completion of tuberculosis (TB) treatment remain problematic in many high-burden countries. 99DOTS is a low-cost digital adherence technology that could increase TB treatment completion.
We conducted a pragmatic stepped-wedge cluster-randomized trial including all adults treated for drug-susceptible pulmonary TB at 18 health facilities across Uganda over 8 months (1 December 2018-31 July 2019). Facilities were randomized to switch from routine (control period) to 99DOTS-based (intervention period) TB treatment supervision in consecutive months. Patients were allocated to the control or intervention period based on which facility they attended and their treatment start date. Health facility staff and patients were not blinded to the intervention. The primary outcome was TB treatment completion. Due to the pragmatic nature of the trial, the primary analysis was done according to intention-to-treat (ITT) and per protocol (PP) principles. This trial is registered with the Pan African Clinical Trials Registry (PACTR201808609844917). Of 1,913 eligible patients at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively), 38.0% were women, mean (SD) age was 39.4 (14.4) years, 46.8% were HIV-infected, and most (91.4%) had newly diagnosed TB. In total, 463 (52.0%) patients were enrolled on 99DOTS during the intervention period. In the ITT analysis, the odds of treatment success were similar in the intervention and control periods (adjusted odds ratio [aOR] 1.04, 95% CI 0.68-1.58, p = 0.87). The odds of treatment success did not increase in the intervention period for either men (aOR 1.24, 95% CI 0.73-2.10) or women (aOR 0.67, 95% CI 0.35-1.29), or for either patients with HIV infection (aOR 1.51, 95% CI 0.81-2.85) or without HIV infection (aOR 0.78, 95% CI 0.46-1.32). In the PP analysis, the 99DOTS-based intervention increased the odds of treatment success (aOR 2.89, 95% CI 1.57-5.33, p = 0.001). The odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were similarly improved in PP but not ITT analyses. Study limitations include the likelihood of selection bias in the PP analysis, inability to verify medication dosing in either arm, and incomplete implementation of some components of the intervention.
99DOTS-based treatment supervision did not improve treatment outcomes in the overall study population. However, similar treatment outcomes were achieved during the control and intervention periods, and those patients enrolled on 99DOTS achieved high treatment completion. 99DOTS-based treatment supervision could be a viable alternative to directly observed therapy for a substantial proportion of patients with TB.
Pan-African Clinical Trials Registry (PACTR201808609844917).
在许多高负担国家，结核病（TB）治疗的依从性和完成率仍然存在问题。99DOTS 是一种低成本的数字依从性技术，可以提高结核病治疗的完成率。
我们进行了一项实用的分步楔形群随机试验，包括在乌干达 18 个卫生机构治疗的所有对药物敏感的肺结核成年患者，持续 8 个月（2018 年 12 月 1 日至 2019 年 7 月 31 日）。设施被随机分配在连续的月份内从常规（对照期）切换到基于 99DOTS 的（干预期）结核病治疗监督。患者根据他们就诊的设施和治疗开始日期被分配到对照组或干预组。卫生机构工作人员和患者对干预措施并不盲目。主要结局是结核病治疗完成情况。由于试验的实用性，主要分析根据意向治疗（ITT）和方案（PP）原则进行。这项试验在泛非临床试验注册处（PACTR201808609844917）注册。在 18 个卫生机构的 1913 名合格患者中（分别为对照组和干预组的 1022 名和 891 名），38.0%为女性，平均（SD）年龄为 39.4（14.4）岁，46.8%为 HIV 感染者，大多数（91.4%）为新发结核病患者。共有 463 名（52.0%）患者在干预期内登记了 99DOTS。在 ITT 分析中，干预期和对照组的治疗成功率相似（调整后的比值比[aOR]1.04，95%置信区间[CI]0.68-1.58，p=0.87）。对于男性（aOR 1.24，95%CI 0.73-2.10）或女性（aOR 0.67，95%CI 0.35-1.29），或 HIV 感染者（aOR 1.51，95%CI 0.81-2.85）或无 HIV 感染者（aOR 0.78，95%CI 0.46-1.32），干预期内治疗成功率均未增加。在 PP 分析中，基于 99DOTS 的干预增加了治疗成功率（aOR 2.89，95%CI 1.57-5.33，p=0.001）。在 PP 但不在 ITT 分析中，强化期治疗的完成率和失访率的可能性也得到了类似的改善。研究局限性包括 PP 分析中存在选择偏倚的可能性，无法在任何一臂中验证药物剂量，以及干预措施的某些组成部分实施不完整。
基于 99DOTS 的治疗监督并没有改善整个研究人群的治疗结果。然而，在对照组和干预组中实现了相似的治疗结果，并且那些登记了 99DOTS 的患者实现了很高的治疗完成率。基于 99DOTS 的治疗监督可以作为结核病患者的一种可行的替代直接观察治疗的方法。
泛非临床试验注册处（PACTR201808609844917）。
