Ignite Creation Date:
2024-10-25 @ 7:56 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06526221
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-23
Brief Title:
Evaluating Urine Isoniazid Testing to Detect Nonadherence to Tuberculosis Medications in India
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Evaluating Urine Isoniazid Testing for Tuberculosis Disease in India to Detect Medication Nonadherence and Improve Treatment Outcomes
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 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 Indias 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
Detailed Description:
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 outcomes2 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 197 95CI 17-234 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 12 95 CI 101-14
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-eg 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 we performed one unannounced home visit for each participant during TB therapy to conduct urine testing We 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 39 increased odds of death and 38 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 ie 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
We propose conducting translational research involving clinical behavioural and implementation science to evaluate the use of urine isoniazid testing in the TB program Our 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 our 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
We have the following specific aims
Aim 1 To assess the agreement between urine test results collected at prescheduled clinic in comparison to unannounced home visits
Summary of this aim We will enroll a cohort of 900 people starting 6-month drug-susceptible TB therapy For each participant to enable comparison of clinic and home samples we will conduct 1 urine test at a scheduled clinic visit and 1 urine test at an unannounced home visit during each of the intensive first 2 months early continuation second 2 months and late continuation last 2 months treatment phases
Aim 2 To assess the relationship between nonadherence by urine testing and subsequent TB outcomes
Summary of this aim We will follow the Aim 1 cohort participants through the completion of TB treatment which usually takes 6 months and then for 12 months after treatment and assess the following unfavorable outcomes death treatment failure loss to follow-up and TB recurrence We will assess the association between nonadherence by urine testing separately for clinic and home samples and the composite of these unfavorable outcomes primary outcome and with each unfavorable outcome individually secondary outcomes
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-eg 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 we performed one unannounced home visit for each participant during TB therapy to conduct urine testing We 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 39 increased odds of death and 38 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 ie 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
We propose conducting translational research involving clinical behavioural and implementation science to evaluate the use of urine isoniazid testing in the TB program Our 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 our 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
We have the following specific aims
Aim 1 To assess the agreement between urine test results collected at prescheduled clinic in comparison to unannounced home visits
Summary of this aim We will enroll a cohort of 900 people starting 6-month drug-susceptible TB therapy For each participant to enable comparison of clinic and home samples we will conduct 1 urine test at a scheduled clinic visit and 1 urine test at an unannounced home visit during each of the intensive first 2 months early continuation second 2 months and late continuation last 2 months treatment phases
Aim 2 To assess the relationship between nonadherence by urine testing and subsequent TB outcomes
Summary of this aim We will follow the Aim 1 cohort participants through the completion of TB treatment which usually takes 6 months and then for 12 months after treatment and assess the following unfavorable outcomes death treatment failure loss to follow-up and TB recurrence We will assess the association between nonadherence by urine testing separately for clinic and home samples and the composite of these unfavorable outcomes primary outcome and with each unfavorable outcome individually secondary outcomes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None