GeneXpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB)

University of California San Francisco (UCSF)

Status: Completed

Conditions: Tuberculosis, Pulmonary; Rifampicin Resistant Tuberculosis

Treatments: Device: GeneXpert I; Other: Performance Feedback; Behavioral: Process re-design

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03044158

R01HL130192 (U.S. NIH Grant/Contract)

PACTR201610001763265 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 10,644 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10,644 participants in 2 patient groups

Control group

No Intervention group

Description:

Onsite ZN or LED fluorescence microscopy + hub-based GeneXpert testing per existing protocols

Intervention

Experimental group

Description:

Onsite molecular testing for TB with GeneXpert I + process redesign to facilitate same-day TB diagnosis and treatment + performance feedback

Treatment:

Behavioral: Process re-design

Other: Performance Feedback

Device: GeneXpert I