Optimizing Clinical Outcomes in HIV-Infected Adults & Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stewart Reid, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02043080
First received: January 16, 2014
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

This is a study to evaluate Xpert MTB/RIF as the first-line TB diagnostic test in HIV-infected adults and paediatric patients as a means to obtain faster, more accurate TB diagnosis.


Condition Intervention
Tuberculosis Diagnosis
HIV
Other: Xpert MTB/RIF Tuberculosis diagnostic tool

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: CIDRZ 1201 - Optimizing Clinical Outcomes in HIV-Infected Adults & Children Using Xpert MTB/RIF in Zambia

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase [ Time Frame: within 4 weeks of initiation ] [ Designated as safety issue: No ]
    proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase, using mycobacterial culture as the reference standard, and the feasibility and cost effectiveness of Xpert MTB/RIF in this setting


Secondary Outcome Measures:
  • Clinical outcomes of subjects screened using the Xpert MTB/RIF algorithm compared to existing standard of care. [ Time Frame: 3 and 6 months post TB-screening ] [ Designated as safety issue: No ]

    Clinical outcomes to be compared include (but are not limited to):

    ART treatment start date CD4 response TB treatment outcomes at 6 months post-diagnosis Mortality Co-morbidities Other Opportunistic Infections Characteristics of TB patients who initially test Xpert negative (Xpert- /Culture + patients)



Other Outcome Measures:
  • Diagnostic performance of Xpert MTB/RIF [ Time Frame: screening visit, 3 and 6 months post screening ] [ Designated as safety issue: No ]
    Sensitivity, specificity, positive and negative predictive values of TB diagnosis with Xpert MTB/RIF compared to culture will be calculated.


Estimated Enrollment: 2816
Study Start Date: August 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard of Care including sputum smear and Chest x-ray
HIV-infected adult and pediatric TB suspects screened for TB according to current standard of care
Experimental: Xpert MTB/RIF, sputum, chest xray and TB culture
HIV-infected adult and pediatric TB suspects screened for TB using the Xpert MTB/RIF algorithm which include chest x-ray, sputum TB culture
Other: Xpert MTB/RIF Tuberculosis diagnostic tool
This is s new diagnostic tool that has been approved by WHO for the diagnosis of TB in HIV-infected patients in resource limited settings
Other Name: Gene Xpert MTB RIF (Cepheid Inc)

Detailed Description:

This study will evaluate Xpert Mycobacterium Tuberculosis/Rifampicin (MTB/RIF) as the first-line Tuberculosis (TB) diagnostic test in Human Immunodeficiency Virus (HIV)-infected adults and paediatric patients in peri-urban settings and determine its impact on accurate case detection and treatment initiation in these settings. In addition, the Determine TB-Lipoarabinomannan (LAM) Ag® will be used to model added diagnostic value when used alone or in combination with Xpert MTB/RIF, within the TB diagnostic algorithm for HIV infected patients in Zambia.

A quasi-experimental "before-after" study design will be used at two similar peri-urban district hospitals. Each site will initially implement the Standard of Care (SOC) phase, in which a prospective cohort of HIV-infected adult and paediatric TB suspects will be screened for TB according to the current standard of care in Zambian HIV care clinics. This will be followed by a 4-week "intervention wash-out" period to allow completion of the diagnostic work-up of all patients recruited during the last month of the SOC phase.

The second phase (Xpert MTB/RIF phase) will start immediately following the "intervention wash-out" period. In this phase, a second cohort of HIV-infected adult and paediatric TB suspects will be screened for TB using the Xpert MTB/RIF algorithm. Each phase will last approximately 6 months, or until the target sample size for adults is reached. Mycobacterial culture will be performed during the study to confirm TB diagnosis and determine whether appropriate treatment was given. "Appropriate treatment" means the patient was initiated on ATT within 4 weeks of screening initiation for culture-positive patients or a correct diagnosis of not having TB in culture-negative patients. Culture results will be released from the CIDRZ Lab for patient care as soon as results are available.

During both study phases participants will be asked to submit a urine sample for testing with the Determine TB-LAM Ag® assay. Urine specimens will be collected at the study site and all procedures will be carried out at the CIDRZ Central Laboratory in Lusaka using standard laboratory protocols and quality assurance procedures. Since Determine TB-LAM Ag® has not yet been endorsed by the World Health Organization (WHO) nor approved by the Zambian Ministry of Health for TB diagnosis, results from the Determine TB-LAM Ag® assay will not be used for patient care.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 15 years or above ("Adult"), or less than 15 years old ("Child") ;
  • HIV-infected and enrolled in HIV care at Chongwe and Kafue District Hospitals
  • Intends to continue receiving care at the district hospital for at least 6 months.
  • TB suspects according to Zambian National Guidelines [31] ;
  • Willing to provide signed informed consent (or parental consent, if the participant is under 18);
  • Willing (or parent or guardian willing) to provide locator information and allow contact by phone or home visit

Exclusion Criteria:

  • Diagnosed with TB within the last 6 months or taken TB treatment in the last 3 months
  • Enrolled in another study which might interfere with study objectives (ex. TB-HAART)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02043080

Contacts
Contact: Margaret Kasaro, MBChB 260 0963223210 magaret.kasaro@cidrz.org

Locations
Zambia
Centre for Infectious Disease Research in Zambia Recruiting
Lusaka, Zambia
Contact: Nzali Kancheya, MBChB, MMED    260 977779700      
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Stewart Reid, MD University of North Carolina
  More Information

Additional Information:
Publications:
Marlowe, E.M., et al., Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol, 2011. 49(4): P. 1621-3.

Responsible Party: Stewart Reid, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02043080     History of Changes
Other Study ID Numbers: 12-1402, XXXXXXX
Study First Received: January 16, 2014
Last Updated: August 7, 2014
Health Authority: Zambia: Research Ethics Committee
Zambia: Ministry of Health
United States: Federal Government
United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Tuberculosis
HIV
Xpert MTB/RIF
Determine TB-LAM
UNC
Zambia
Cost Effectiveness Analysis Curve
Centre for Infectious Disease Research in Zambia

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 21, 2014