Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection A Randomized Trial
Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection A Randomized Trial
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DOI：
10.7326/m17-1150
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发表时间：
2017-11-21
影响因子：
39.2
通讯作者：
Borisov, Andrey S.
中科院分区：
文献类型：
--
作者：
Belknap, Robert;Holland, David;Borisov, Andrey S.
背景：扩大潜伏性结核病的治疗对减少全球活动性疾病很重要。异烟肼和利福喷丁每周1次，共12次有效，但由于需要直接观察而受到限制。目的：比较每周一次异烟肼和利福喷丁自行给药与直接观察治疗的完成度和安全性。设计：一项开放标签的4期随机临床试验，设计为15%边际的非劣效性研究。75%或更多的研究患者来自美国，进行预先指定的亚组分析。(临床试验。地点：美国、西班牙、香港和南非的肺结核门诊诊所。参与者：1002名成人（年龄>= 18岁）推荐治疗潜伏性结核感染。干预：参与者每周接受一次异烟肼和利福喷丁的直接观察，自我给药并每月监测，或自我给药并每周短信提醒和每月监测。测量：主要终点是治疗完成，定义为在16周内服用11次或更多剂量，使用临床文献和直接观察的药丸计数，以及自我报告、药丸计数和自我给药的药物事件监测设备进行测量。主要的次要结局是不良事件。结果：中位年龄为36岁，48%的参与者为女性，77%的参与者在美国网站注册。指导观察组治疗完成率为87.2% (95% CI, 83.1% ~ 90.5%)，自我给药组为74.0% (CI, 68.9% ~ 78.6%)，自我给药加提醒组为76.4% （CI, 71.3% ~ 80.8%）。在美国，治疗完成率分别为85.4% （CI， 80.4%至89.4%）、77.9% （CI， 72.7%至82.6%）和76.7% （CI， 70.9%至81.7%）。在美国，没有提醒的自我治疗不逊于直接观察；没有其他比较符合非劣效性标准。发生了一些与药物相关的不良事件，并且各组之间相似。局限性：在南非登记的潜伏性肺结核感染患者不会得到常规的规划治疗。结论：这些结果支持在美国使用每周一次的自我给药异烟肼和利福喷丁治疗潜伏性结核感染，在类似的情况下，当直接观察不可行时，可以考虑使用这种治疗。
Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation.Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation.Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials. gov: NCT01582711)Setting: Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa.Participants: 1002 adults (aged >= 18 years) recommended for treatment of latent tuberculosis infection.Intervention: Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring.Measurements: The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication eventmonitoring devices for self-administration. The main secondary outcome was adverse events.Results: Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U. S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the directobservation group, 74.0% (CI, 68.9% to 78.6%) in the selfadministration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration-with-reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups.Limitation: Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically.Conclusion: These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible.