Effect of Xpert MTB/RIF on Patient Outcomes

Study Overview
=================
Brief Summary
-----------------
A parallel-group prospective cohort study among adult persons living with HIV/AIDS to study the effect of a new TB diagnostic test, Xpert MTB/RIF on: 1) TB case detection; 2) time to TB diagnosis and TB treatment; 3) presumptive TB patient drop-out from the TB diagnostic cascade before starting TB treatment; and 4) loss to follow-up after initiation of TB treatment.

Detailed Description
-----------------
The Centre for Infectious Disease Research in Zambia (CIDRZ) in collaboration with the Zambian National TB Program (NTP) and the Ministry of Health (MOH) will provide near point-of-care Xpert testing at a high-volume anti-retroviral treatment (ART) clinic in Lusaka, Zambia. A total 892 study participants will be enrolled into two parallel cohorts-an Xpert and a standard of care (SOC) cohort over a 7-month period. The Xpert cohort will enrol participants at the health centre implementing Xpert. The SOC cohort will enrol participants from one health centre offering the standard of care (sputum smear microscopy plus clinical evaluation). A parallel-group prospective cohort study will be conducted by following participants in one cohort from each site for 210 days from the time of sputum submission, allowing sufficient person-time to observe all outcomes of interest, including completion of a standard course of ATT as well as patient drop-out and loss to follow-up. A systematic facility assessment survey using an adapted version of the WHO Service Availability and Readiness Assessment tool will be conducted. Key informants will be interviewed.

Official Title
-----------------
Z 31411 - The Effect of Xpert MTB/RIF on Patient Health Outcomes and Empirical TB Treatment Among Persons Living With HIV/AIDS: A Parallel-Group Prospective Cohort Study Under Real-World Conditions in Lusaka, Zambia

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Device: Xpert


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to spontaneously expectorate at least 2 sputum samples, in accordance with NTP guidelines Intend to continue receiving care at the respective study sites for at least 7 months Willing to provide locator information and allow contact by phone or home visit in the case of loss to follow up after initiating ATT Exclusion Criteria: Received TB treatment within 60 days prior to enrolment and/or were diagnosed with TB within the last 6 months Cannot spontaneously expectorate sputum Are already enrolled in another study with might interfere with implementation of this study protocol Provided a sputum sample that results in a contaminated TB culture result A key informant will be eligible for inclusion in the SARA facility survey component of the study if they meet the following criteria: 18 years of age or older clinic staff member at either Chilenje Health Centre or Chelstone Health Centre have previously been attached to, or are otherwise familiar with, departments offering HIV, TB and/or laboratory health services Exclusion criteria: -unwilling or unable to provide verbal informed consent in English

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Xpert cohort<br>HIV-positive presumptive TB patients tested for TB using Xpert MTB/RIF assay (fluorescence microscopy and TB culture also done to serve as reference standard) | Device: Xpert<br>* The Xpert MTB/RIF assay is a nucleic acid amplification (NAA) test that uses a disposable cartridge with the GeneXpert Instrument System<br>* Other names: Xpert MTB/RIF assay;|
| Standard of Care cohort<br>HIV-positive presumptive TB patients tested for TB using standard of care testing (sputum smear microscopy plus clinical evaluation) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Culture-positive patient drop-out before accessing treatment | For both cohorts, the proportion of patients not started on TB treatment by 210 days post-enrolment will be assessed. | From study enrolment through confirmed drop out date at or before 210-days post enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to TB treatment |  | time in days from study enrolment to initiation of anti-TB therapy (ATT) (through 210 days post-enrolment) | 
| Percentage of participants who receive TB treatment within 14 days of enrolment (effect of Xpert on the accuracy of TB diagnosis) | sensitivity of empirical TB diagnosis and treatment will be defined as the percentage of participants who received TB treatment within 14 days of enrolment among all those with a positive culture but negative or unavailable result for SM (for the SOC cohort), or negative or unavailable SM plus Xpert (for the Xpert cohort) | study enrolment to 14 days of enrolment | 
| Percentage of participants who did not receive TB treatment 14 days post-enrolment (effect of Xpert on the accuracy of TB diagnosis) | the specificity of empirical treatment will be defined as the percentage of participants who did not receive TB treatment 14 days post-enrolment among all those with a negative culture and negative or unavailable result for SM (in the SOC cohort), or negative or unavailable result for SM plus Xpert (in the Xpert cohort) | study enrolment to 14 days of enrolment | 
| Time to TB Diagnosis | The World Health Organization definition of a TB case will be used | average of 28 days | 
| Number of TB patients lost to follow-up |  | The number of patients will be measured as time in days from study enrolment to confirmed drop out (confirmed as failure noted at 3 and 6 month chart review) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Extra-pulmonary tuberculosis, multiple drug resistant tuberculosis, mycobacterium tuberculosis, human immunodeficiency virus