Clinical trial NCT02043080: Optimizing Clinical Outcomes in HIV-Infected Adults & Children
Official title: CIDRZ 1201 - Optimizing Clinical Outcomes in HIV-Infected Adults & Children Using Xpert MTB/RIF in Zambia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis Diagnosis
HIV
Keywords: Tuberculosis
HIV
Xpert MTB/RIF
Determine TB-LAM
UNC
Zambia
Cost Effectiveness Analysis Curve
Centre for Infectious Disease Research in Zambia
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2014-01-23
Enrollment: 1436
Sex: ALL
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility 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)

Primary outcomes:
measure: Proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase
timeFrame: within 4 weeks of initiation
Secondary outcomes:
measure: Clinical outcomes of subjects screened using the Xpert MTB/RIF algorithm compared to existing standard of care.
timeFrame: 3 and 6 months post TB-screening
Other outcomes:
measure: Diagnostic performance of Xpert MTB/RIF
timeFrame: screening visit, 3 and 6 months post screening
Locations:
city: Lusaka
country: Zambia
facility: Centre for Infectious Disease Research in Zambia
Study officials:
affiliation: University of North Carolina
name: Stewart Reid, MD
role: PRINCIPAL_INVESTIGATOR
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