Assessing Diagnostics At Point-of-care for Tuberculosis

Study Overview
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Brief Summary
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Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) study seeks to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests.

Detailed Description
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The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) seeks to identify and rigorously assess promising, design-locked point-of-care (POC) tuberculosis (TB) diagnostic tests (hereafter referred to as novel tests) in clinical studies conducted in settings of intended use. Rapid diagnosis and effective treatment are critical for improving patient outcomes and reducing TB transmission. However, nearly one-third of people with TB are not diagnosed or reported to public health authorities.The different types of tests required to reduce this diagnostic gap have been described in the form of target product profiles (TPPs) defined by the World Health Organization (WHO). The highest priority TPP is that for a point-of-care, non-sputum biomarker-based test to facilitate rapid TB diagnosis using easily accessible samples (i.e., a biomarker-based diagnostic test). The ADAPT study will evaluate the sensitivity, specificity and yield of novel diagnostic tests against a reference standard including sputum Xpert® Mycobacterium tuberculosis/Rifampicin (MTB/RIF) Ultra and sputum mycobacterial culture among adolescents and adults with presumptive TB (based on having TB symptoms, or TB risk factor + positive TB screening test) presenting to outpatient health facilities in high burden countries. In addition, the usability and acceptability of novel TB diagnostic tests will be assessed through direct observations and surveys of routine health workers.

Official Title
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Supporting, Mobilizing and Accelerating Research for Tuberculosis Elimination (SMART4TB)- Technical Area (TA) 1: Diagnostics- Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT)

Conditions
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Tuberculosis

Intervention / Treatment
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* Diagnostic Test: Tongue swab-based molecular assays


Participation Criteria
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Eligibility Criteria
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Novel TB triage and diagnostic tests: Inclusion Criteria- The investigators will include non-hospitalized adults (age ≥ 12 years) with either: cough ≥2 weeks' duration, a commonly accepted criterion for identifying people with presumed pulmonary TB (to facilitate standardization across sites and comparison of test performance across sub-groups; OR risk factors for which TB screening is recommended (HIV infection, self-reported close contact, history of mining work). People with risk factors will be included if they screen positive for TB based on WHO-recommended screening tools as specified below: Positive TB screening definitions by risk factor: People Living with Human Immunodeficiency Virus (PLHIV) (Risk Factor): C Reactive Protein (CRP) >5 mg/dL OR abnormal chest x-ray (CXR) Self-reported Close Contact (Risk Factor): abnormal CXR History of mining work (Risk Factor): abnormal CXR Exclusion Criteria- Completed latent or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively); Have taken any medication with anti-mycobacterial activity (including fluoroquinolones) for any reason, within 2 weeks of study entry (to reduce false-negatives); Reside >20km from the study site or are unwilling to return for follow-up visits; OR Are unwilling to provide informed consent Assessment of the usability of novel TB tests: Inclusion Criteria- The investigators will include health workers at each clinical site who are: aged ≥18 years; AND involved in routine TB testing (collecting specimens for or performing TB tests). Exclusion Criteria- The investigators will exclude staff who are: 1) unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evaluation of various novel TB triage and diagnostic tests<br>For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB. The investigators aim to enroll 450 participants per year at each of three enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability. | Diagnostic Test: Tongue swab-based molecular assays<br>* The investigators will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion with positive index test result among participants with tuberculosis (TB) | Sensitivity - Number with positive index test result/(Number with positive or negative index t test result) among participants with TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results) | 2 years | 
| Proportion with negative index test result among participants without tuberculosis (TB) | Specificity - Number with negative index test results/(Number with positive or negative index t test result) among participants without TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Diagnostics, Global Health