Global Consortium for Drug-resistant Tuberculosis Diagnostics

Study Overview
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Brief Summary
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The goal of this study is to evaluate time to diagnosis for three assays (line probe, pyrosequencing, and Microscopic Observation Drug Susceptibility Assay [MODS]) to detect resistance to first and second-line anti-tuberculosis (TB) drugs in Mycobacterium tuberculosis (Mtb) strains in 7 days or less, allowing for rapid diagnosis of extensively drug-resistant TB (XDR-TB).

Detailed Description
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The goals of this study are to test, fine tune, and compare three tests (line probe, pyrosequencing, MODS assays) to rapidly detect Mycobacterium tuberculosis (Mtb) strains that are resistant to first and second-line anti-tuberculosis (TB) drugs allowing for rapid diagnosis of Extensively Drug-Resistant Tuberculosis (XDR-TB). Primary Specific Aims Aim 1: To reduce the average XDR-TB detection time from months to a week. Aim 2: To determine agreement between rapid tests and standard drug susceptibility testing (DST) results. Aim 3: To identify the genetic basis of discordant results from Aim 2. Aim 4: To characterize genotypic, phenotypic and epidemiological features, as well as geographical relationships, of XDR-TB strains compared to other drug-resistant and susceptible strains. Secondary Aims Aim 1: Cost-effectiveness study. The costs associated with rapid-test implementation will be compared with the performance of the new tests to rapidly and accurately detect drug resistance and XDR-TB. Aim 2: To determine the predictive value of resistance-associated mutations in determining sputum culture conversion. The investigators hypothesize that analysis of the genotypic basis of anti-TB drug resistance will allow for the development of improved rapid molecular drug susceptibility tests that will detect resistance to fluoroquinolones and injectable anti-TB drugs and reduce the current XDR-TB diagnosis time of up to three months to less than seven days.

Official Title
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Global Consortium for Drug-resistant Tuberculosis Diagnostics

Conditions
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Tuberculosis, Tuberculosis, Multidrug-Resistant

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 5 years of age Known to be acid fast bacilli (AFB) sputum smear-positive, 1+ or greater (within prior 14 days), positive on GeneXpert, or present clinically with high suspicion of active TB and: Had previously received >1 month of treatment for a prior TB episode or Were failing TB treatment with positive sputum smear or culture after ≥3 months of a standard TB treatment or Had had close contact with a known drug-resistant TB case or Were newly diagnosed with multi-drug resistant TB (MDR-TB) within the last 30 days or Were previously diagnosed with MDR-TB and failed TB treatment with positive sputum smear or culture after ≥3 months of a standard MDR-TB treatment regimen Provided informed consent or had ability and willingness of subject or legal guardian/representative to provide informed consent Exclusion Criteria: Institutionalized Unable to provide at least 7.5ml sputum (1st and 2nd samples combined) Had results from second line DST performed within the last 3 months

Ages Eligible for Study
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Minimum Age: 5 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients at risk for drug-resistant TB<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to completion of rapid diagnostic assays | Time to completion was calculated from date of initial sputum collection to completion of each rapid diagnostic assay. Time frame for analysis of all results was from date of first patient recruited till 21 weeks after last patient recruited (total 83 weeks). | Up to 83 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Multi-drug resistant tuberculosis, Extensively drug-resistant tuberculosis, Drug-resistant tuberculosis, Mycobacterial Growth Indicator Tube Drug Susceptibility Test, Line Probe Assay, Microscopic Observation Drug Susceptibility Assay, Pyrosequencing