GeneXpert Performance Evaluation for Linkage to Tuberculosis Care

NCT ID: NCT03044158

Last Updated: 2025-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10644 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-22
• Study Completion Date: 2022-07-31

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.

Conditions

Tuberculosis, Pulmonary; Rifampicin Resistant Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Control group

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention

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

Group Type: EXPERIMENTAL

GeneXpert I

Intervention Type: DEVICE

Onsite molecular testing with GeneXpert I as a replacement for microscopy

Process re-design

Intervention Type: BEHAVIORAL

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.

Performance Feedback

Intervention Type: OTHER

Feedback of TB diagnostic evaluation quality indicators to health center staff

Interventions

GeneXpert I

Onsite molecular testing with GeneXpert I as a replacement for microscopy

Intervention Type: DEVICE

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.

Intervention Type: BEHAVIORAL

Performance Feedback

Feedback of TB diagnostic evaluation quality indicators to health center staff

Intervention Type: OTHER

Other Intervention Names

GeneXpert

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Makerere University

OTHER

Sponsor Role: collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adithya Cattamanchi, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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, , Uganda

Countries

Uganda

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

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Document Type: Informed Consent Form

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Other Identifiers

PACTR201610001763265

Identifier Type: REGISTRY

Identifier Source: secondary_id

R01HL130192

Identifier Type: NIH

Identifier Source: secondary_id

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R01HL130192

Identifier Type: NIH

Identifier Source: org_study_id

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