Xpert MTB/RIF Test in the Diagnosis of Pulmonary Tuberculosis

Study Overview
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Brief Summary
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Currently in Taiwan, most clinicians use sputum smear and culture for the diagnosis of pulmonary tuberculosis (TB) and apply nucleic acid amplification (NAA) test in a selected manner. In 2013, the World Health Organization issued conditional recommendation that Xpert MTB/RIF may be used rather than conventional microscopy and culture as the initial diagnostic test in all adults suspected of having TB. The newly published Taiwan guidelines for TB diagnosis and treatment has recommended NAA test, together with smear and culture, as the initial diagnostic test in individuals suspected of having TB. The investigators conduct a prospective study to investigate the use of Xpert MTB/RIF as the initial diagnostic test of pulmonary TB under a pragmatic trial design.

Detailed Description
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In this study the investigators will respect current practice in the use of NAA in the diagnosis of pulmonary TB. Clinicians may have ordered NAA as the initial diagnostic test in adults suspected of having pulmonary TB (group A, Immediate NAA by clinician), and the investigators will not intervene. For patients who do not have NAA as the initial diagnostic test, the investigators will use random permuted blocks to randomize these participants into two groups. One group will have immediate Xpert test (intervention group) as the initial diagnostic test and another group will continue usual care without immediate Xpert test (control group). Group A (Immediate NAA by clinician): NAA as the initial diagnostic test for pulmonary TB requested by clinicians. Group B (Immediate NAA as intervention): NAA as the initial diagnostic test for pulmonary TB not requested by clinicians, but is performed as intervention in this study (intervention group). Group C (No immediate NAA): NAA as the initial diagnostic test for pulmonary TB not requested by clinicians, and is not performed as the initial diagnostic test in this study (control group). NAA may be ordered at a later point in time by clinicians as an add-on test after sputum smear microscopy. The investigators will assess pulmonary TB cases detected in all groups regarding The interval between sputum examinations and initiation of ant-TB treatment. The proportion of culture confirmed pulmonary TB among all pulmonary TB cases notified. The proportion of TB patients who are advised to stop anti-TB treatment before completion of a treatment course. Outcome of tuberculosis treatment, including patients who die before anti-TB treatment. Among patients with NAA as the initial diagnostic test (Group A and Group B), the investigators will investigate Performance (sensitivity, specificity and predictive values) of NAA in the diagnosis of culture positive pulmonary TB. The incremental yield of the second and third smear in patients who have both NAA test and smear microscopy as the initial diagnostic test, aiming to determine the contribution of the second and third smear in the diagnosis of pulmonary TB. The proportion of NAA positive cases who were culture negative.

Official Title
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Xpert MTB/RIF Test as the Initial Diagnostic Test in the Diagnosis of Pulmonary Tuberculosis: a Pragmatic Trial

Conditions
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Pulmonary Tuberculosis Confirmation by Culture

Intervention / Treatment
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* Diagnostic Test: Xpert MTB/RIF test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All presumptive tuberculosis cases who have sputum examinations for the diagnosis of pulmonary TB Exclusion Criteria: Tuberculosis cases who have been on treatment for 14 or more days who have sputum examinations for follow-up

Ages Eligible for Study
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Minimum Age: 20 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pragmatic trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate NAA by clinician<br>Nucleic acid amplification test requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB | Diagnostic Test: Xpert MTB/RIF test<br>* Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB<br>* Other names: nucleic acid amplification test;|
| Experimental: Immediate NAA as intervention<br>Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, but Xpert MTB/RIF is performed as intervention in this study (intervention group) | Diagnostic Test: Xpert MTB/RIF test<br>* Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB<br>* Other names: nucleic acid amplification test;|
| No Intervention: No immediate NAA<br>Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, and Xpert MTB/RIF is not performed as the initial diagnostic test in this study (control group). Nucleic acid amplification test may be ordered at a later point in time by clinicians as an add-on test after sputum smear microscopy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diagnostic turnaround time | The interval between sputum examinations and initiation of ant-TB treatment | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| culture positive pulmonary TB | The proportion of culture confirmed pulmonary TB among pulmonary TB cases notified | through study completion, an average of 1 year | 
| change diagnosis | The proportion of TB patients who are advised to stop anti-TB treatment before completion of a treatment course | 12 months after the initiation of anti-tuberculosis treatment | 
| treatment outcomes | The proportion of patients who die before anti-TB treatment, who are successfully treated, who died during treatment, who are loss-to-follow-up, who have treatment failure and who are transferred out | 12 months after the initiation of anti-tuberculosis treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Xpert MTB/RIF, diagnostic turnaround time