Evaluating Urine Isoniazid Testing to Detect Nonadherence to Tuberculosis Medications in India
NCT Number: NCT06526221
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Tuberculosis, Pulmonary|Medication Adherence
Interventions: DIAGNOSTIC_TEST: Urine isoniazid testing (IsoScreen test)
Sponsor: Tufts University
Collaborators: Tuberculosis Research Centre, India|Massachusetts General Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 900
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: HEALTH_SERVICES_RESEARCH
Start Date: 2025-04-01
Completion Date: 2028-09-30

Summary:
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, we 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. Our 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, we 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, we 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.

Primary Outcome Measures: Composite unfavorable tuberculosis treatment outcome, 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 outcome will be assessed during the course of TB treatment (usually about 6 months) and for the 12 months after TB treatment completion.
Secondary Outcome Measures: Loss to follow-up during tuberculosis treatment, This outcome will be defined as treatment interruption or being unable to contact a participant for \>4 weeks., This outcome will be assessed during the course of TB treatment (usually about 6 months).|Treatment failure (i.e., failure of tuberculosis treatment), A participant (person with TB) whose sputum smear or culture is positive at month 5 or later during treatment., This outcome will be assessed during the course of TB treatment (usually about 6 months).|Death, Mortality from any cause, his outcome will be assessed during the course of TB treatment (usually about 6 months) and for the 12 months after TB treatment completion.|Tuberculosis recurrence, Among study participants who achieved tuberculosis treatment completion, this will be defined as a positive sputum culture or an empirical (clinical) diagnosis of TB by healthcare providers in India's National TB Elimination Programme during the 12 months after a participant completed tuberculosis treatment., This outcome will be assessed during the 12 months after completion of tuberculosis treamtent.