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

NCT06526221 | Not Yet Recruiting DMC

• 1 other identifier: STUDY00004944
• Study Type: interventional
• Target: 900
• Locations: 0 countries
• Sites: N/A

Brief 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

Outcome Measures

Primary Outcomes (1)

• The proportion of participants experiencing a 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 will be reported as the number and proportion of participants experiencing one of the unfavorable outcomes, among all participants enrolled in the cohort study.

  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 Outcomes (4)

• 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.

Study Arms (1)

Urine isoniazid testing (intervention arm)

EXPERIMENTAL

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).

Diagnostic Test: Urine isoniazid testing (IsoScreen test)

Interventions

Urine isoniazid testing (IsoScreen test) DIAGNOSTIC_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).

Urine isoniazid testing (intervention arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• + years of age,
• presumed or confirmed drug-susceptible pulmonary TB (with or without a previous TB history), and
• taking an isoniazid-containing TB regimen.

You may not qualify if:

• inability to provide informed consent, or

Sponsors & Collaborators

• Tufts University: lead
• Tuberculosis Research Centre, India: collaborator
• Massachusetts General Hospital: collaborator

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Medication Adherence

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Central Study Contacts

Ramnath Subbaraman, MD

CONTACT

6175044335; ramnath.subbaraman@tufts.edu

Karikalan Nagarajan, PhD

CONTACT

+91-7299226582; karikalan.n@icmr.gov.in

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Based on NIH definitions, this is considered a clinical trial given that there is prospective assignment of an intervention (i.e., urine isoniazid testing) to evaluate medication adherence. As such, this could be considered a single group/arm study with prospective assignment of the intervention to all study participants.

Study Record Dates

• First Submitted: July 23, 2024
• First Posted: July 29, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: January 6, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be made available as soon as possible or at the time of associated publication, whichever comes first.
• Access Criteria: The NIAID Clinical Trials Data Repository provides metadata, persistent identifiers (i.e., digital object identifier), and long-term access. This repository is supported by the National Institute of Allergy and Infectious Diseases and datasets are available under a data access request process.