Clinical Trial of Short Course vs. INH for LTBI in Jail

描述（由申请人提供）：监禁人口中的结核病（TB）是一个严重问题，因为很大比例的囚犯具有潜伏性结核病感染（LTBI）和发展为活动性疾病的高风险。在监狱中完成LTBI治疗并不成功，主要是因为囚犯经常在完成6-9个月的每日异烟肼标准治疗之前就被释放了，而且因为他们在社区中完成治疗的比率很低。LTBI的有效治疗因治疗时间和药物毒性而变得复杂。LTBI的短期治疗可能会解决这个问题，但它们还没有得到充分的研究，以回答有关副作用、完成率和总体成本的问题。我们建议进行一项双臂、开放标签随机试验，以测试短期治疗对监禁囚犯LTBI的效果；每天服用利福平，持续4个月，而INH每周服用两次，持续9个月。972名同意和登记的参与者将在监狱中接受直接观察治疗（DOT）。该研究方案包括与结核病诊所的联系，以便在释放后进行DOT，并在整个治疗过程中进行密切的临床和实验室监测。参与者将在入组后的一年内，在监狱和释放后进行随访，以衡量三个结果：毒性、依从性和成本效益。研究小组将分析导致停药的毒性，并检查其他预测因素，如年龄、酒精使用和乙型肝炎和丙型肝炎。通过完成治疗来衡量的依从性，将由研究小组进行比较，并检查其他预测因素，包括社会人口统计学变量、坚持的意图和住房的稳定性。成本效益将按研究小组进行比较，并将根据预防结核病病例的成本来衡量，使用管理和监测护理的直接成本以及重新开始治疗的成本在这一重新遏制率高的人群中进行计算。

DESCRIPTION (provided by applicant): Tuberculosis (TB) in incarcerated populations is a serious problem, due to the large proportion of inmates who are at high risk of having latent tuberculosis infection (LTBI) and developing active disease. Completion of treatment of LTBI has not been successful in jails, mainly because inmates are frequently released before finishing a 6-9 month course of standard therapy with daily isoniazid (INH), and because they have low rates of completing therapy in the community. Effective treatment of LTBI is complicated by length of therapy and toxicity of the drugs used against L TBI. Short-course therapies for LTBI may address this problem but they have not been studied adequately to answer questions about side effects, completion rates, and overall cost. We propose a two arm, open label randomized trial to test the effects of a short-course therapy for LTBI in jailed inmates; rifampin given daily for 4 months as compared to INH given twice weekly for 9 months. A sample of 972 consented and enrolled participants will be administered directly observed therapy (DOT) in jail. The study protocol includes links to the TB Clinic for post-release DOT, and close clinical and laboratory monitoring throughout the course of therapy. Participants will be followed, in jail and after release, for one year after enrollment, to measure three outcomes: toxicity, adherence, and cost-effectiveness. Toxicity leading to stopping drug will be analyzed by study group, and other predictors will be examined, such as age, alcohol use and hepatitis B and C. Adherence, measured by completion of therapy, will be compared by study group, and other predictors will be examined, including sociodemographic variables, intent to adhere, and stability of housing. Cost-effectiveness will be compared by study group and will be calculated using direct costs of administering and monitoring care and costs of re-starting care in this population with a high rate of re-arrest, measured against the cost of prevented cases of TB. Short course regimens are promising in the inmate population to treat LTBI and eliminate risk of progression to active disease. This study will answer questions about the safety of rifampin compared directly to INH. Analysis of completion of therapy and cost-effectiveness of this regimen will provide important information for policy change in the way L TBI is managed in jail.