Triage Test for All Oral DR TB Regimen: T2RiAD study (TRiAD Study)

Ongoing transmission of drug-resistant tuberculosis (DR-TB) remains a major obstacle to the United Nations (UN) End-TB strategy.

To reach targets of 90% reduction in tuberculosis (TB) incidence and mortality by 2035, implementation of new and improved diagnostic and treatment approaches are urgently warranted.

This study will adopt a Triage-and-Treat approach using novel TB diagnostic technologies to guide implementation of short, all-oral regimens for DR-TB.

The TRIAD consortia include leading DR-TB scientists from South Africa, Nigeria, Tanzania, Ethiopia, the Netherlands, Switzerland and Italy that will evaluate implementation of novel approaches aimed at addressing DR-TB.

The TriAD study is a multi-center, multi-country Prospective Pragmatic Cohort study assessing the effectiveness, feasibility, acceptability, and cost-effectiveness of implementing the GeneXpert MTB/XDR (Xpert XDR; Cepheid) assay for rapid triage-and-treatment of DR-TB.

The proposed study aims to screen approximately 4800 GeneXpert MTB/RIF or Ultra positive (irrespective of rifampicin resistance status) patients from 9 study sites in South Africa, Nigeria and Ethiopia to enroll 880 RR and 400 HR patients.

The Xpert XDR assay that tests for resistance to isoniazid, fluoroquinolones and second-line injectable agents will be implemented as a reflex test to provide rapid genotypic susceptibility testing for DR-TB detection.

All patients must test positive for Mycobacterium Tuberculosis and those with rifampicin resistance will be enrolled in Cohort 1 (n=880) while those with isoniazid mono-resistance will be enrolled in Cohort 2 (n=400).

The Xpert XDR assay result will be used for selection of appropriate, evidence-based all-oral DR-TB treatment regimens of shortest possible duration.

In parallel, the molecular bacterial load assay will be used to provide bacillary load monitoring over the course of treatment to assess real-time treatment response.

Outcome data among patients enrolled in Cohort 1 of this study will be compared to historic outcome data of similar DR-TB patients diagnosed and managed at study sites 12-18 months before the proposed prospective study.

Diagnostic data of Xpert XDR assay screening for HR, pre-XDR and XDR will inform optimal placement Xpert XDR within the current DR-TB diagnostic algorithm.

Furthermore, operational and cost-effectiveness research generated in this study will be used to inform policies and guidelines for programmatic implementation of the triage-and-treat model. The TriAD study will provide an approach for improving diagnosis and treatment of every patient with DR-TB.

This study will generate real-world evidence, guiding delivery and uptake of novel diagnostics and all-oral regimens, that has potential to alter the course of the DR-TB epidemic.