Evaluating Urine Isoniazid Testing for Tuberculosis Disease in India to Detect Medication Nonadherence and Improve Treatment Outcomes
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 900
- 试验地点
- 2
- 主要终点
- The proportion of participants experiencing a composite unfavorable tuberculosis treatment outcome
研究概览
简要总结
Tuberculosis (TB) is the leading infectious cause of death globally. India has the largest TB epidemic, accounting for one-quarter of cases and one-third of TB deaths worldwide. Nonadherence to medications is a central challenge in TB care leading to increased death, disease recurrence, and drug resistance. Despite its importance, detecting nonadherence in routine care is challenging, as current measurement approaches are inaccurate, not person-centered, or ineffective at improving outcomes. Early and accurate detection of nonadherence may serve as an entry point for differentiated care, in which people with TB at risk for poor outcomes can be given intensified interventions. Urine isoniazid testing is a validated, low-cost, point-of-care, and direct adherence measure that may be predictive of TB outcomes and therefore serve as an ideal triage test to enable differentiated care. However, to integrate urine testing into routine care, research is needed to: (1) understand how the test performs at scheduled clinic visits, (2) gain a rich understanding of root causes of nonadherence to better leverage urine test results, and (3) identify barriers and facilitators to implementation. In this study, the investigators propose conducting a 900 participant prospective cohort study with translational research involving clinical, behavioral, and implementation science to facilitate integration of urine isoniazid testing into India's national TB program. The investigators' central hypothesis is that urine testing can be integrated into routine care to facilitate early and accurate identification of people with TB who are likely to suffer poor outcomes, including death and TB recurrence. In Aim 1, the investigators will assess the accuracy of urine test results assessed at scheduled clinic visits in comparison to those assessed at unannounced home visits. In Aim 2, the investigators will assess the relationship between nonadherence detected by urine testing and subsequent unfavorable TB outcomes of death, loss to follow-up, treatment failure, and post-treatment TB recurrence.. This study proposal aims to develop an innovative but pragmatic strategy for early identification of TB medication nonadherence that is feasible in low- and middle-income countries with a high TB burden.
详细描述
Tuberculosis (TB) is the leading infectious cause of death globally. India has the largest TB epidemic, accounting for one-quarter of cases and one-third of global TB deaths. Nonadherence to TB medications is associated with increased death, TB recurrence, and drug resistance. Specifically, missing >10% of doses is associated with six times greater risk of poor TB outcomes.2 The association between nonadherence to TB medications and emergence of drug resistance is one of the most concerning from a public health perspective. For example, one study found that nonadherence to TB therapy was associated with independent elevated risk of acquiring drug resistance (adjusted odds ratio 19.7, 95%CI 1.7-234). Another study found that, among people being treated for multidrug-resistant (MDR) TB, each additional month in which a patient failed to take 80% of their prescribed medication doses was associated with elevated risk of developing extensively drug-resistant (XDR) TB (adjusted hazard ratio 1.2, 95% CI 1.01-1.4).
Despite its importance, detecting nonadherence in routine care is challenging, especially as TB programs in low- and middle-income countries (LMICs) have moved away from directly observed therapy. Our research shows indirect measures-e.g., cellphone-based technology, pill counts, and patient-reported measures-miss detecting >30% of people with TB who are nonadherent by urine isoniazid testing.
Urine isoniazid testing is a low-cost, validated, direct point-of-care adherence measure that is predictive of TB outcomes. In a 650-participant cohort study in India, one unannounced home visit was conducted for each participant during TB therapy to conduct urine testing. That study found: (1) nonadherence was common by urine testing, with 18% of participants having missed more than 1 dose, and (2) negative urine test results were associated with 3.9 increased odds of death and 3.8 increased odds of loss to follow-up from treatment.
While urine testing has benefits, further research is needed to evaluate its uses under TB programs setting First, urine testing may perform differently in clinic as compared to unannounced home visits, as people with TB may modify adherence behavior in anticipation of scheduled clinic visits. Research is needed to understand how well testing at clinic visits represents adherence and predicts TB outcomes. Second, research is needed to understand reasons for nonadherence (i.e., negative urine test results) to inform personalized interventions for differentiated care. Third, implementation science research is needed to evaluate the use of urine testing in routine care in a manner that could lead to sustained use and impact.
The investigators propose conducting translational research involving clinical, behavioural, and implementation science to evaluate the use of urine isoniazid testing in the TB program. The investigators' central hypothesis is that urine testing could be useful within the routine care to facilitate early and accurate identification of people with TB who are likely to suffer poor outcomes, including death and TB recurrence. If this hypothesis is correct, the urine assay could serve as a triage test for developing differentiated care strategies, in which people at risk for poor outcomes are identified early and given intensified care
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18+ years of age,
- •presumed or confirmed drug-susceptible pulmonary TB (with or without a previous TB history), and
- •taking an isoniazid-containing TB regimen.
排除标准
- •inability to provide informed consent, or
- •drug-resistant TB diagnosis or switch to another non-isoniazid-containing regimen (Note that this second exclusion criteria may result in retrospective exclusion from the study).
研究组 & 干预措施
Urine isoniazid testing (intervention arm)
This is the only study group/arm in this study. Participants in this study arm will receive urine isoniazid testing using the IsoScreen test in the TB clinic at monthly clinical and medication refill visits at month 1, 2, 3, 4, and 5 (5 times total). The will also undergo urine isoniazid testing using the IsoScreen test at home visits after months 1, 3, and 5 of treatment (3 times total).
干预措施: Urine isoniazid testing (IsoScreen test) (Diagnostic Test)
结局指标
主要结局
The proportion of participants experiencing a composite unfavorable tuberculosis treatment outcome
时间窗: This outcome will be assessed during the course of TB treatment (usually about 6 months) and for the 12 months after TB treatment completion.
The primary outcome will comprise the composite of: (1) loss to follow-up during treatment, (2) treatment failure, (3) death during the on-treatment or post-treatment period, and (4) TB recurrence. This will be reported as the number and proportion of participants experiencing one of the unfavorable outcomes, among all participants enrolled in the cohort study.
次要结局
- The proportion of participants lost to follow-up during tuberculosis treatment(This outcome will be assessed during the course of TB treatment (usually about 6 months).)
- The proportion of participants experiencing treatment failure (i.e., failure of tuberculosis treatment)(This outcome will be assessed during the course of TB treatment (usually about 6 months).)
- The proportion of participants experiencing death(his outcome will be assessed during the course of TB treatment (usually about 6 months) and for the 12 months after TB treatment completion.)
- The proportion of participants experiencing tuberculosis recurrence(This outcome will be assessed during the 12 months after completion of tuberculosis treamtent.)