GeneXpert Performance Evaluation for Linkage to Tuberculosis Care

Tuberculosis, Pulmonary Clinical Trial

— XPEL-TB  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03044158
• Other study ID #: R01HL130192
• Secondary ID: PACTR20161000176
• Status: Completed
• Phase: N/A
• Start date: October 22, 2018
• Est. completion date: July 31, 2022

Study information

• Verified date: April 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10644
• Est. completion date: July 31, 2022
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Rifampicin Resistant Tuberculosis
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Device:
• GeneXpert I
Onsite molecular testing with GeneXpert I as a replacement for microscopy

Behavioral:
• Process re-design
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.

Other:
• Performance Feedback
Feedback of TB diagnostic evaluation quality indicators to health center staff

Locations

Country	Name	City	State
Uganda	St Francis Njeru Health Center III	Buikwe
Uganda	Busana Health Center III	Busana
Uganda	Busesa Health Center IV	Busesa
Uganda	Buwama Health Center III	Buwama
Uganda	Iganga TC	Iganga
Uganda	Bukulula Health Center IV	Kalungu
Uganda	Nazigo Health Center III	Kayunga
Uganda	Kiganda Health Center IV	Kiganda
Uganda	Kira Health Center III	Kira
Uganda	Lugasa Health Center III	Lugala
Uganda	Bishop Asili Health Center	Luwero
Uganda	Kinoni Health Center III	Lwengo
Uganda	Kityerera Health Center IV	Mayuge
Uganda	Malongo Health Center III	Mayuge
Uganda	Mayuge Health Center III	Mayuge
Uganda	Wabulungu Health Center III	Mayuge
Uganda	Malangala Health Center III	Mityana
Uganda	Lwampanga Health Center III	Nakasongola
Uganda	Namungalwe Health Center III	Namungalwe
Uganda	Nankandulo Health Center IV	Nankandulo

Sponsors (6)

Lead Sponsor	Collaborator
University of California, San Francisco	Johns Hopkins Bloomberg School of Public Health, London School of Hygiene and Tropical Medicine, Makerere University, National Heart, Lung, and Blood Institute (NHLBI), Yale University

Country where clinical trial is conducted

Uganda, 

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* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number referred for TB testing	Effectiveness outcome.	Within 2 weeks of initial sputum submission
Secondary	Number diagnosed with microbiologically-confirmed TB	Effectiveness outcome.	Within 2 weeks of initial sputum submission
Secondary	Number suspected/diagnosed with RIF-resistant TB	Effectiveness outcome.	Within 2 weeks of initial sputum submission
Secondary	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.
Secondary	Number treated for TB	Effectiveness outcome.	Within 2 weeks of initial sputum submission
Secondary	Number of patients enrolled	Effectiveness outcome.	Within 2 weeks of initial sputum submission
Secondary	Number diagnosed and treated for microbiologically-confirmed TB	Effectiveness outcome.	Within 2 weeks of initial sputum submission
Secondary	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.
Secondary	Number diagnosed AND completing treatment	Effectiveness outcome.	Days from initial health center visit to treatment outcome, up to 2 years.
Secondary	Number who died within 6 months	Effectiveness outcome.	Days from initial health center visit to treatment outcome, up to 6 months.