Clinical trial NCT03044158: GeneXpert Performance Evaluation for Linkage to Tuberculosis Care
Official title: GeneXpert Performance Evaluation for Linkage to Tuberculosis Care: The XPEL-TB Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis, Pulmonary
Rifampicin Resistant Tuberculosis
Keywords: tuberculosis
implementation science
point-of-care
diagnostics
GeneXpert
Uganda
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Makerere University
name: Johns Hopkins Bloomberg School of Public Health
name: London School of Hygiene and Tropical Medicine
name: Yale University
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-02-06
Enrollment: 10644
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number Treated for Microbiologically-confirmed TB Within 14 Days After Presentation to the Health Center for TB Evaluation
timeFrame: Within 14 days after presentation to the health center for tuberculosis evaluation
Secondary outcomes:
measure: Number Diagnosed With Microbiologically-confirmed TB
timeFrame: Within 14 days after presentation to the health center for tuberculosis evaluation
measure: Time to Microbiologically-confirmed TB
timeFrame: Within 6 months of presentation to the health center for tuberculosis evaluation
measure: Number Treated for TB
timeFrame: Within 14 days of presentation to the health center for tuberculosis evaluation
measure: Time-to-treatment of Microbiologically-confirmed TB
timeFrame: Days from initial health center visit to initiation of treatment if diagnosed, up to 6 months.
measure: Number Who Died Within 6 Months
timeFrame: Within 6 months of presentation to the health center for tuberculosis evaluation
measure: Number of Patients Enrolled
timeFrame: Presentation to the health center for tuberculosis evaluation during the 16-month study time frame
measure: Number Tested for TB According to National Guidelines
timeFrame: Within 6 months of presentation to the health center for tuberculosis evaluation
measure: Number Suspected/Diagnosed With Rifampin-resistant TB
timeFrame: Within 6 months of presentation to the health center for tuberculosis evaluation
measure: Number Diagnosed and Treated for Microbiologically-confirmed TB
timeFrame: On the same-day of presentation to the health center for tuberculosis evaluation
measure: Number Diagnosed AND Treated for TB
timeFrame: On the same-day of presentation to the health center for tuberculosis evaluation
Other outcomes:
Locations:
city: Buikwe
country: Uganda
facility: St Francis Njeru Health Center III
city: Busana
country: Uganda
facility: Busana Health Center III
city: Busesa
country: Uganda
facility: Busesa Health Center IV
city: Buwama
country: Uganda
facility: Buwama Health Center III
city: Iganga
country: Uganda
facility: Iganga TC
city: Kalungu
country: Uganda
facility: Bukulula Health Center IV
city: Kayunga
country: Uganda
facility: Nazigo Health Center III
city: Kiganda
country: Uganda
facility: Kiganda Health Center IV
city: Kira
country: Uganda
facility: Kira Health Center III
city: Lugala
country: Uganda
facility: Lugasa Health Center III
city: Luwero
country: Uganda
facility: Bishop Asili Health Center
city: Lwengo
country: Uganda
facility: Kinoni Health Center III
city: Mayuge
country: Uganda
facility: Kityerera Health Center IV
city: Mayuge
country: Uganda
facility: Malongo Health Center III
city: Mayuge
country: Uganda
facility: Mayuge Health Center III
city: Mayuge
country: Uganda
facility: Wabulungu Health Center III
city: Mityana
country: Uganda
facility: Malangala Health Center III
city: Nakasongola
country: Uganda
facility: Lwampanga Health Center III
city: Namungalwe
country: Uganda
facility: Namungalwe Health Center III
city: Nankandulo
country: Uganda
facility: Nankandulo Health Center IV
Study officials:
affiliation: University of California, San Francisco
name: Adithya Cattamanchi, MD
role: PRINCIPAL_INVESTIGATOR
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