Evaluating Urine Isoniazid Testing to Detect Nonadherence to Tuberculosis Medications in India

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, 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.

Conditions

• Tuberculosis, Pulmonary
• Medication Adherence

Interventions

DIAGNOSTIC_TEST

Urine isoniazid testing (IsoScreen test)

Developed by Arkansas' Public Health Service in the 1970s, this test detects metabolites of isoniazid, a drug present in drug-susceptible TB regimens. IsoScreen (GFC Diagnostics, UK) is a commercial version of the Arkansas method with reagents enclosed in a plastic vial, into which 2mL of urine can be injected with a syringe. If the urine contains isoniazid, reagents turn purple/blue (suggesting a dose was taken in the last 24 hours or appropriate adherence) or green (suggesting a dose was taken 24-48 hours before or one missed dose). A yellow result (no color change) suggests medication has not been taken for \>48 hours (two or more missed doses).

Sponsors & Collaborators

• Tuberculosis Research Centre, India

  collaborator OTHER_GOV

• Massachusetts General Hospital

  collaborator OTHER

• Tufts University

  lead OTHER

Study Design

Allocation

NA

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-04-01

Primary Completion

2028-09-30

Completion

2028-09-30