Tuberculosis DiagnosisNCT02043080
Optimizing Clinical Outcomes in HIV-Infected Adults & Children
A study testing Xpert MTB/RIF Tuberculosis diagnostic tool in people with Tuberculosis Diagnosis and HIV, run by University of North Carolina, Chapel Hill at 1 site in Zambia.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 99 years
- Conditions the study is for
- Tuberculosis Diagnosis, HIV
- What is being tested?
- Xpert MTB/RIF Tuberculosis diagnostic tool
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,436 participants
- Where
- 1 siteZambia
- Study dates
- Aug 2012to Apr 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CIDRZ 1201 - Optimizing Clinical Outcomes in HIV-Infected Adults & Children Using Xpert MTB/RIF in Zambia
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.
Read the 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.
- Conditions
- Tuberculosis Diagnosis, HIV
- Being tested
- Xpert MTB/RIF Tuberculosis diagnostic tool
- Keywords
- Tuberculosis, HIV, Xpert MTB/RIF, Determine TB-LAM, UNC, Zambia, Cost Effectiveness Analysis Curve, Centre for Infectious Disease Research in Zambia
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xpert MTB/RIF Tuberculosis diagnostic toolOther
Also called Gene Xpert MTB RIF (Cepheid Inc)
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
| Study group | Role | What they receive |
|---|---|---|
| SOC: sputum smear and Chest x-ray | No intervention | HIV-infected adult and pediatric TB suspects screened for TB according to current standard of care |
| Xpert MTB/RIF, sputum, chest xray &TB culture | Experimental | 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 Receives: Other: Xpert MTB/RIF Tuberculosis diagnostic tool |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: within 4 weeks of initiation
Secondary outcomes (1)
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)
Measured: 3 and 6 months post TB-screening
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2014 (estimated)
- Study startAug 2012
- Primary completionMar 2016
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis DiagnosisStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,436 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Stewart Reid, MD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02043080
- Sponsor's protocol ID
- 12-1402
- Status last verified
- May 2017
- First submitted
- 16 Jan 2014
- Last updated
- 3 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
World Health Organization, Global Tuberculosis Control: WHO Report 2011. 2011:Geneva, Switzerland.
Ayles H, Schaap A, Nota A, Sismanidis C, Tembwe R, De Haas P, Muyoyeta M, Beyers N; Peter Godfrey-Faussett for the ZAMSTAR Study Team. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS One. 2009;4(5):e5602. doi: 10.1371/journal.pone.0005602. Epub 2009 May 19.
PubMed 19440346Reid, 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.
Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008 Oct 1;22(15):1897-908. doi: 10.1097/QAD.0b013e32830007cd.
PubMed 18784453Lawn SD, Kranzer K, Wood R. Antiretroviral therapy for control of the HIV-associated tuberculosis epidemic in resource-limited settings. Clin Chest Med. 2009 Dec;30(4):685-99, viii. doi: 10.1016/j.ccm.2009.08.010.
PubMed 19925961Henostroza, G., Unpublished work: Enhancing TB Screening in Zambian Prisons. 2011.
Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009 Mar;9(3):173-84. doi: 10.1016/S1473-3099(09)70043-X.
PubMed 19246021Dawson R, Masuka P, Edwards DJ, Bateman ED, Bekker LG, Wood R, Lawn SD. Chest radiograph reading and recording system: evaluation for tuberculosis screening in patients with advanced HIV. Int J Tuberc Lung Dis. 2010 Jan;14(1):52-8.
PubMed 20003695Walls T, Shingadia D. Global epidemiology of paediatric tuberculosis. J Infect. 2004 Jan;48(1):13-22. doi: 10.1016/s0163-4453(03)00121-x.
PubMed 14667788Hesseling AC, Cotton MF, Jennings T, Whitelaw A, Johnson LF, Eley B, Roux P, Godfrey-Faussett P, Schaaf HS. High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies. Clin Infect Dis. 2009 Jan 1;48(1):108-14. doi: 10.1086/595012.
PubMed 19049436Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis. 2012 Apr 26;12:103. doi: 10.1186/1471-2334-12-103.
PubMed 22536883Lusaka Urban District Health Management Team, Annual Tuberculosis Report. 2009.
Turnbull ER, Kaunda K, Harris JB, Kapata N, Muvwimi MW, Kruuner A, Henostroza G, Reid SE. An evaluation of the performance and acceptability of three LED fluorescent microscopes in Zambia: lessons learnt for scale-up. PLoS One. 2011;6(11):e27125. doi: 10.1371/journal.pone.0027125. Epub 2011 Nov 4.
PubMed 22073271Kang'ombe CT, Harries AD, Ito K, Clark T, Nyirenda TE, Aldis W, Nunn PP, Semba RD, Salaniponi FM. Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB. Int J Tuberc Lung Dis. 2004 Jul;8(7):829-36.
PubMed 15260273Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25;362(8):697-706. doi: 10.1056/NEJMoa0905848.
PubMed 20181971
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CIDRZ 1201 - Optimizing Clinical Outcomes in HIV-Infected Adults & Children Using Xpert MTB/RIF in Zambia
- ClinicalTrials.gov ID
- NCT02043080
- Acronym / sponsor ID
- 12-1402
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,436 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- Aug 2012 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 23 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOC: sputum smear and Chest x-ray | No intervention | –HIV-infected adult and pediatric TB suspects screened for TB according to current standard of care |
| Xpert MTB/RIF, sputum, chest xray &TB culture | Experimental | Other: Xpert MTB/RIF Tuberculosis diagnostic toolHIV-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 |
Who may qualify
- Ages
- Up to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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);
Key exclusion criteria (2 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Xpert MTB/RIF Tuberculosis diagnostic toolAlso: Gene Xpert MTB RIF (Cepheid Inc)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 | Xpert MTB/RIF, sputum, chest xray &TB culture |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2017.
- BackgroundWorld Health Organization, Global Tuberculosis Control: WHO Report 2011. 2011:Geneva, Switzerland.
- Background: PubMed 19440346Ayles H, Schaap A, Nota A, Sismanidis C, Tembwe R, De Haas P, Muyoyeta M, Beyers N; Peter Godfrey-Faussett for the ZAMSTAR Study Team. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS One. 2009;4(5):e5602. doi: 10.1371/journal.pone.0005602. Epub 2009 May 19.
- BackgroundReid, 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.
- Background: PubMed 18784453Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008 Oct 1;22(15):1897-908. doi: 10.1097/QAD.0b013e32830007cd.
- Background: PubMed 19925961Lawn SD, Kranzer K, Wood R. Antiretroviral therapy for control of the HIV-associated tuberculosis epidemic in resource-limited settings. Clin Chest Med. 2009 Dec;30(4):685-99, viii. doi: 10.1016/j.ccm.2009.08.010.
- BackgroundHenostroza, G., Unpublished work: Enhancing TB Screening in Zambian Prisons. 2011.
- Background: PubMed 19246021Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009 Mar;9(3):173-84. doi: 10.1016/S1473-3099(09)70043-X.
- Background: PubMed 20003695Dawson R, Masuka P, Edwards DJ, Bateman ED, Bekker LG, Wood R, Lawn SD. Chest radiograph reading and recording system: evaluation for tuberculosis screening in patients with advanced HIV. Int J Tuberc Lung Dis. 2010 Jan;14(1):52-8.
- Background: PubMed 14667788Walls T, Shingadia D. Global epidemiology of paediatric tuberculosis. J Infect. 2004 Jan;48(1):13-22. doi: 10.1016/s0163-4453(03)00121-x.
- Background: PubMed 19049436Hesseling AC, Cotton MF, Jennings T, Whitelaw A, Johnson LF, Eley B, Roux P, Godfrey-Faussett P, Schaaf HS. High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies. Clin Infect Dis. 2009 Jan 1;48(1):108-14. doi: 10.1086/595012.
- Background: PubMed 22536883Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis. 2012 Apr 26;12:103. doi: 10.1186/1471-2334-12-103.
- BackgroundLusaka Urban District Health Management Team, Annual Tuberculosis Report. 2009.
- University of North Carolina websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stewart Reid, MD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Xpert MTB/RIF Tuberculosis diagnostic tool in people with Tuberculosis Diagnosis and HIV, run by University of North Carolina, Chapel Hill at 1 site in Zambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase (time frame: within 4 weeks of initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02043080, which also lists 38 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2017.