Optimizing Clinical Outcomes in HIV-Infected Adults & Children

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. Read our disclaimer for details. Identifier: NCT02043080
Recruitment Status : Completed
First Posted : January 23, 2014
Last Update Posted : August 3, 2017
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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

Condition or disease Intervention/treatment Phase
Tuberculosis Diagnosis HIV Other: Xpert MTB/RIF Tuberculosis diagnostic tool Not Applicable

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 pediatric 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 pediatric 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 pediatric 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1436 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: CIDRZ 1201 - Optimizing Clinical Outcomes in HIV-Infected Adults & Children Using Xpert MTB/RIF in Zambia
Actual Study Start Date : August 2012
Actual Primary Completion Date : March 2016
Actual Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
No Intervention: SOC: 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 &TB culture
HIV-infected adult and pediatric TB suspects screened for TB using the Xpert MTB/RIF Tuberculosis diagnostic tool (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)

Primary Outcome Measures :
  1. Proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase [ Time Frame: within 4 weeks of initiation ]
    proportions of adult and pediatric 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 :
  1. 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 ]

    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:
  1. Diagnostic performance of Xpert MTB/RIF [ Time Frame: screening visit, 3 and 6 months post screening ]
    Sensitivity, specificity, positive and negative predictive values of TB diagnosis with Xpert MTB/RIF compared to culture will be calculated.

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Ages Eligible for Study:   up to 99 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

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 identifier (NCT number): NCT02043080

Centre for Infectious Disease Research in Zambia
Lusaka, Zambia
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Centers for Disease Control and Prevention
Principal Investigator: Stewart Reid, MD University of North Carolina

Additional Information:
World Health Organization, Global Tuberculosis Control: WHO Report 2011. 2011:Geneva, Switzerland.
Reid, S.E., Unpublished Data: Enhanced TB Screening to determine the prevalence and incidence of TB in a cohort of HIV clinic patients in Lusaka, Zambia. 2012.
Henostroza, G., Unpublished work: Enhancing TB Screening in Zambian Prisons. 2011.
Lusaka Urban District Health Management Team, Annual Tuberculosis Report. 2009.
Blanc, F.-X., et al., Early (2 weeks) vs. late (8 weeks) initiation of highly active antiretroviral treatment (HAART) significantly enhance survival of severely immunosuppressed HIV-infected adults with newly diagnosed tuberculosis: results of the CAMELIA clinical trial. BMC Proceedings, 2011. 5(Suppl 1): p. O11.
World Health Organization, Roadmap for rolling out Xpert MTB/RIF for rapid diagnosis of TB and MDR-TB. 2010.
Zambia Ministry of Health National Tuberculosis and Leprosy Control Programme, Tuberculosis and TB/HIV Manual. 2008: Lusaka.
World Health Organization, Rapid Implementation of the Xpert MTB/RIF diagnostic test: Technical and operational 'How-to' Practical considerations. 2011.
Francis J. Curry National Tuberculosis Center Institutional Consultation Services, Conducting Sputum Induction Safely. 1999.
World Health Organization, Guidelines for cost and cost-effectivness analysis of tuberculosis control. 2002.
Petitti, D., Meta-Analysis, Decision Analysis, and Cost-Effectivness Analysis. Methods for Quantitative Synthesis in Medicine. 2nd edition ed. 2000, New York: Oxford Press.
Drummond MF, S., M.J., Torrance, G.W., O'Brien, B.J., Stoddart, G.L., Methods for the Economic Evaluation of Health Car Programmes. Vol. 3rd edition. 2005: Oxford University Press.

Responsible Party: University of North Carolina, Chapel Hill Identifier: NCT02043080     History of Changes
Other Study ID Numbers: 12-1402
First Posted: January 23, 2014    Key Record Dates
Last Update Posted: August 3, 2017
Last Verified: May 2017

Keywords provided by University of North Carolina, Chapel Hill:
Determine TB-LAM
Cost Effectiveness Analysis Curve
Centre for Infectious Disease Research in Zambia

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