GeneXpert Performance Evaluation for Linkage to Tuberculosis Care

Study Overview
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Brief Summary
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The investigators' overall objective is to assess the effectiveness, implementation and costs of a streamlined TB diagnostic evaluation strategy based around rapid, onsite molecular testing. The intervention strategy was developed based on theory-informed assessment of barriers to TB diagnostic evaluation at community health centers in Uganda and a process of engagement with local stakeholders. It includes: 1) Point-of-care molecular testing using GeneXpert as a replacement for sputum smear microscopy; 2) Re-structuring of clinic-level procedures to facilitate same-day TB diagnosis and treatment; and 3) Quarterly feedback of TB evaluation metrics to health center staff. The investigators' central hypothesis is that the intervention strategy will have high uptake and increase the number of patients diagnosed with and treated for active pulmonary TB. To test this hypothesis, the investigators will conduct a pragmatic cluster-randomized trial at community health centers that provide TB microscopy services in Uganda in partnership with the National TB Program (NTP). The investigators utilize an effectiveness-implementation hybrid design in which, concurrent with the clinical trial, the investigators will conduct nested mixed methods, health economic and modeling studies to assess 1) whether the intervention strategy modifies targeted barriers to TB diagnostic evaluation; 2) fidelity of implementation of the intervention components (i.e, the degree to which intervention components were implemented as intended vs. adapted across sites); and 3) cost-effectiveness and public health impact.

Detailed Description
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Aim 1: To compare patient outcomes at health centers randomized to intervention vs. standard-of-care TB diagnostic evaluation strategies. The investigators will randomize 20 community health centers to continue standard TB evaluation (routine microscopy plus referral of patients for Xpert testing per existing processes of care) or to implement the intervention strategy (1. Onsite molecular testing; 2. Re-structuring clinic-level procedures to facilitate same-day TB diagnosis and treatment; and 3. Performance feedback). The investigators will compare reach and effectiveness based on the numbers and proportions of patients (N=5500) who complete TB testing, are found to have TB, and have treatment initiated within one week of specimen provision. Aim 2: To identify processes and contextual factors that influence the effectiveness and fidelity of the intervention TB diagnostic evaluation strategy. The investigators will use quantitative process metrics to assess the adoption and maintenance over time of the core components of the intervention strategy. The investigators will also collect quantitative and qualitative data to describe the fidelity of implementation of each component and faithfulness to the conceptual model. Aim 3: To compare the costs and epidemiological impact of intervention vs. standard-of-care TB diagnostic evaluation strategies. The investigators will model the incremental costs and cost-effectiveness of intervention relative to standard-of-care TB diagnostic evaluation from the health system and patient perspective. The investigators will then construct an epidemic model of the population-level impact of the intervention strategy on TB incidence and mortality.

Official Title
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GeneXpert Performance Evaluation for Linkage to Tuberculosis Care: The XPEL-TB Trial

Conditions
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Tuberculosis, Pulmonary, Rifampicin Resistant Tuberculosis

Intervention / Treatment
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* Device: GeneXpert I
* Behavioral: Process re-design
* Other: Performance Feedback


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Site-level: Use standard (multi-day) sputum smear microscopy as the primary method of TB diagnosis Site-level: Participate in NTP-sponsored external quality assurance (EQA) for sputum smear microscopy Site-level: Send samples to a district or regional hospital/health center for Xpert testing Patient-level: Initiate evaluation for active TB at a study health center Exclusion Criteria: Site-level: Do not agree to be randomized to standard-of-care vs. intervention arms Site-level: Perform sputum smear examination on <150 patients per year (based on 2015 data) Site-level: Diagnose <15 smear-positive TB cases per year (based on 2015 data) Patient-level: Have sputum collected for monitoring of response to anti-TB therapy Patient-level: Have sputum collected as part of active, community-based case finding (e.g., contact tracing, community outreach campaign) Patient-level: Referred to a study health center for TB treatment after a diagnosis is established elsewhere Patient-level: Started on TB treatment for extra-pulmonary TB only

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Onsite ZN or LED fluorescence microscopy + hub-based GeneXpert testing per existing protocols | |
| Experimental: Intervention<br>Onsite molecular testing for TB with GeneXpert I + process redesign to facilitate same-day TB diagnosis and treatment + performance feedback | Device: GeneXpert I<br>* Onsite molecular testing with GeneXpert I as a replacement for microscopy<br>* Other names: GeneXpert;Behavioral: Process re-design<br>* Research and Uganda NTLP staff will engage health center staff in a discussion of how to re-organize clinical, laboratory and pharmacy services to enable same-day TB diagnosis and treatment.<br>Other: Performance Feedback<br>* Feedback of TB diagnostic evaluation quality indicators to health center staff<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number treated for microbiologically-confirmed TB within two weeks of referral for sputum-based testing | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number referred for TB testing | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 
| Number diagnosed with microbiologically-confirmed TB | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 
| Number suspected/diagnosed with RIF-resistant TB | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 
| Time to microbiologically-confirmed TB | Effectiveness outcome. Time-to-diagnosis if microbiologically-confirmed TB. | Days from initial sputum submission to being diagnosed, up to 60 days. | 
| Number treated for TB | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 
| Number of patients enrolled | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 
| Number diagnosed and treated for microbiologically-confirmed TB | Effectiveness outcome. | Within 2 weeks of initial sputum submission | 
| Time-to-treatment of microbiologically-confirmed TB | Effectiveness outcome. Time-to-treatment if microbiologically-confirmed TB and treated. | Days from initial health center visit to initiation of treatment if diagnosed, up to 1 year. | 
| Number diagnosed AND completing treatment | Effectiveness outcome. | Days from initial health center visit to treatment outcome, up to 2 years. | 
| Number who died within 6 months | Effectiveness outcome. | Days from initial health center visit to treatment outcome, up to 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tuberculosis, implementation science, point-of-care, diagnostics, GeneXpert, Uganda