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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03044158
Recruitment Status : Recruiting
First Posted : February 6, 2017
Last Update Posted : June 7, 2019
Sponsor:
Collaborators:
Makerere University
Johns Hopkins Bloomberg School of Public Health
London School of Hygiene and Tropical Medicine
Yale University
Information provided by (Responsible Party):
University of California, San Francisco

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.

Condition or disease Intervention/treatment Phase
Tuberculosis, Pulmonary Rifampicin Resistant Tuberculosis Device: GeneXpert I Behavioral: Process re-design Other: Performance Feedback Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: GeneXpert Performance Evaluation for Linkage to Tuberculosis Care: The XPEL-TB Trial
Actual Study Start Date : October 22, 2018
Estimated Primary Completion Date : March 1, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
No Intervention: Control group
Onsite ZN or LED fluorescence microscopy + hub-based GeneXpert testing per existing protocols
Experimental: Intervention
Onsite molecular testing for TB with GeneXpert I + process redesign to facilitate same-day TB diagnosis and treatment + performance feedback
Device: GeneXpert I
Onsite molecular testing with GeneXpert I as a replacement for microscopy
Other Name: GeneXpert

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




Primary Outcome Measures :
  1. Number treated for microbiologically-confirmed TB within two weeks of referral for sputum-based testing [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.


Secondary Outcome Measures :
  1. Number referred for TB testing [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.

  2. Number diagnosed with microbiologically-confirmed TB [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.

  3. Number suspected/diagnosed with RIF-resistant TB [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.

  4. Time to microbiologically-confirmed TB [ Time Frame: Days from initial sputum submission to being diagnosed, up to 60 days. ]
    Effectiveness outcome. Time-to-diagnosis if microbiologically-confirmed TB.

  5. Number treated for TB [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.

  6. Number of patients enrolled [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.

  7. Number diagnosed and treated for microbiologically-confirmed TB [ Time Frame: Within 2 weeks of initial sputum submission ]
    Effectiveness outcome.

  8. Time-to-treatment of microbiologically-confirmed TB [ Time Frame: Days from initial health center visit to initiation of treatment if diagnosed, up to 1 year. ]
    Effectiveness outcome. Time-to-treatment if microbiologically-confirmed TB and treated.

  9. Number diagnosed AND completing treatment [ Time Frame: Days from initial health center visit to treatment outcome, up to 2 years. ]
    Effectiveness outcome.

  10. Number who died within 6 months [ Time Frame: Days from initial health center visit to treatment outcome, up to 6 months. ]
    Effectiveness outcome.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03044158


Contacts
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Contact: Adithya Cattamanchi, MD +1-415-206-5489 adithya.cattamanchi@ucsf.edu

Locations
Show Show 20 study locations
Sponsors and Collaborators
University of California, San Francisco
Makerere University
Johns Hopkins Bloomberg School of Public Health
London School of Hygiene and Tropical Medicine
Yale University
Investigators
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Principal Investigator: Adithya Cattamanchi, MD University of California, San Francisco

Publications:
Chandrasekaran V, Ramachandran R, Cunningham J, Balasubramaniun R, Thomas A, Sudha G, et al. Factors leading to tuberculosis diagnostic drop-out and delayed treatment initiation in Chennai, India. Int J Tuberc Lung Dis. 2005;9:172.
Den Boon S, Semitala F, Cattamanchi A, Walter N, Worodria W, Joloba M, Huang L, Davis JL. Impact of patient drop-out on the effective sensitivity of smear microscopy strategies. Am J Respir Crit Care Med 2010;181:A2258.
Miller C, Haguma P, Ochom E, Ross J, Davis JL, Cattamanchi A, Katamba A. Costs associated with tuberculosis evaluation in rural Uganda. 43rd Union World Conference on Lung Health; Kuala Lumpur, Malaysia 2012.
WHO. Global strategy and targets for tuberculosis prevention, care and control after 2015. Geneva, Switzerland: World Health Organization, 2013 EB134/12.
WHO. WHO monitoring of Xpert MTB/RIF roll-out. Available at: http://www.who.int/tb/areas-of-work/laboratory/mtb-rif-rollout/en/ [cited 2015 January 15].
Churchyard GJ, on behalf of the Xtend study team. Xpert MTB/RIF vs microscopy as the first line TB test in South Africa: mortality, yield, initial loss to follow up and proportion treated. The Xtend Study. Conference on Retroviruses and Opportunistic Infections; Boston, USA: Available at: http://www.stoptb.org/wg/gli/assets/documents/M6/Churchyard%20-%20XTEND%20study.pdf; 2014.
Cepheid. GeneXpert Omni: The True Point of Care Molecular Diagnostic System: Cepheid Inc; 2015. Available from: http://www.cepheid.com/us/genexpert-omni.
Ajzen I. The theory of planned behavior. Organizational Behavior and Human Decision Processes. 1991;50:179-211.
Green LW, Krueter M. Health Program Planning - An Educational and Ecological Approach. 4th ed. Philadelphia, USA: McGraw-Hill; 2005.
Hayes RJ, Moulton LH. Cluster Randomized Trials. Boca Raton, Florida, USA: CRC Press; 2009.

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03044158    
Other Study ID Numbers: R01HL130192 ( U.S. NIH Grant/Contract )
PACTR201610001763265 ( Registry Identifier: Pan African Clinical Trials Registry )
First Posted: February 6, 2017    Key Record Dates
Last Update Posted: June 7, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Provided upon request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of California, San Francisco:
tuberculosis
implementation science
point-of-care
diagnostics
GeneXpert
Uganda
Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections