Xpert MTB/XDR Clinical Evaluation Trial

Study Overview
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Brief Summary
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FIND and partners intend to address the need for a multi- and extensively drug-resistant tuberculosis (M/XDR-TB) diagnostic solution for patients in settings with a high burden of drug-resistant tuberculosis (DR-TB) though the development, evaluation and introduction of an Xpert MTB/XDR assay

Official Title
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Multicentre Clinical Trial to Assess the Performance of the Xpert MTB/XDR Assay for INH- and Second-line Resistance Detection

Conditions
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Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant

Intervention / Treatment
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* Device: Cepheid Gene Xpert MTB/XDR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Age 18 years or above; Symptoms suggesting pulmonary TB, i.e. persistent cough (generally ≥3 weeks or as per local definition of TB suspect), and at least one of the following: Previously received >1 month of treatment for a prior TB episode or Failing TB treatment with positive sputum smear or culture after ≥3 months of a standard TB treatment or Had close contact with a known drug-resistant TB case or Newly diagnosed with MDR-TB within the last 30 days or 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 Patients meeting the above criteria will be screened by Xpert MTB/RIF or Xpert MTB/RIF Ultra. TB patients meeting the following criteria will be included in the study: A clear Mtb-positive and RIF-resistant or RIF-sensitive result by Xpert MTB/RIF or Xpert MTB/RIF Ultra Provision of informed consent; Production of an adequate quantity (>3mL) of sputum Exclusion Criteria: Participants will be excluded from the study if informed consent is not provided.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TB case detection Group<br>Patients with pulmonary TB symptoms and at least one DR-TB risk factor will be screened by Xpert MTB/RIF or Ultra. Patients with a clear TB-positive and RIF-resistant or RIF-sensitive result by Xpert MTB/RIF or Ultra and who consent to study procedures will be tested by Xpert MTB/XDR. | Device: Cepheid Gene Xpert MTB/XDR<br>* The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) is an integrated, automated, cartridge-based system for MDR-TB diagnosis that uses the GeneXpert instrument platform. WHO confirmed evidence to support the widespread use of the Xpert MTB/RIF assay in 2010 and the assay has since been widely used in TB programs, but it is only capable of identifying Mycobacterium tuberculosis (Mtb) and detecting RIF resistance. The Xpert MTB/XDR assay will be evaluated for INH and second-line resistance detection, and to recommend its use in diverse clinical settings. The focus of this protocol is the multicentre clinical evaluation.<br>|
| RIF-resistance MTB Group<br>An anticipated 316 additional RIF-resistant patients, as detected by Xpert MTB. /RIF, will be enrolled in this study to evaluate sensitivity and specificity of the Xpert MTB/XDR test against strains with other potential drug-resistance mutations. | Device: Cepheid Gene Xpert MTB/XDR<br>* The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) is an integrated, automated, cartridge-based system for MDR-TB diagnosis that uses the GeneXpert instrument platform. WHO confirmed evidence to support the widespread use of the Xpert MTB/RIF assay in 2010 and the assay has since been widely used in TB programs, but it is only capable of identifying Mycobacterium tuberculosis (Mtb) and detecting RIF resistance. The Xpert MTB/XDR assay will be evaluated for INH and second-line resistance detection, and to recommend its use in diverse clinical settings. The focus of this protocol is the multicentre clinical evaluation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate the diagnostic accuracy of the Xpert MTB/XDR assay for INH and ETH resistance detection | Sensitivity and specificity estimates for INH and ETH resistance detection | Day 1 | 
| Estimate the diagnostic accuracy of the Xpert MTB/XDR assay for fluoroquinolone resistance detection | Sensitivity and specificity estimates for fluoroquinolone resistance detection | Day 1 | 
| Estimate the diagnostic accuracy of the Xpert MTB/XDR assay for second-line injectable resistance detection | Sensitivity and specificity estimates for second-line injectable resistance detection | Day 1 |