Optimizing Clinical Outcomes in HIV-Infected Adults & Children

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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CIDRZ 1201 - Optimizing Clinical Outcomes in HIV-Infected Adults & Children Using Xpert MTB/RIF in Zambia

Conditions
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Tuberculosis Diagnosis, HIV

Intervention / Treatment
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* Other: Xpert MTB/RIF Tuberculosis diagnostic tool


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: SOC: sputum smear and Chest x-ray<br>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<br>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<br>* 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<br>* Other names: Gene Xpert MTB RIF (Cepheid Inc);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase | 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 | within 4 weeks of initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcomes of subjects screened using the Xpert MTB/RIF algorithm compared to existing standard of care. | 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) | 3 and 6 months post TB-screening | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, HIV, Xpert MTB/RIF, Determine TB-LAM, UNC, Zambia, Cost Effectiveness Analysis Curve, Centre for Infectious Disease Research in Zambia