Ignite Creation Date:
2024-05-06 @ 2:13 AM
Last Modification Date:
2024-10-26 @ 11:15 AM
Study NCT ID:
NCT01990274
Status:
COMPLETED
Last Update Posted:
2015-11-25
First Post:
2013-10-24
Brief Title:
The Utility of Intensified Case Finding Combined With a Package of Novel TB Diagnostics Using a Mobile Clinic in Africa
Sponsor:
University of Cape Town
Organization:
University of Cape Town
Study Overview
Official Title:
The Utility of Intensified Case Finding Combined With a Package of Novel TB Diagnostics Using a Mobile Clinic in Africa- a Randomized Controlled Trial XACT
Status:
COMPLETED
Status Verified Date:
2015-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
XACT
Brief Summary:
The purpose of this study is to compare two different methods of intensified tuberculosis TB case finding in the community These methods all involve the use of a mobile clinic to reach people with TB symptoms who are not able to readily access clinic services A standard diagnostics package consisting of smear microscopy and culture with smear result available the next day will be compared with a novel diagnostics package involving point-of-care sputum GeneXpert MTBRIF performed at a mobile or conventional clinic with same day result sputum culture and lateral flow urinary lipoarabinomannan LAM testing in HIV ve subjects only The primary outcome is a comparison between the number of culture ve subjects on TB treatment in each group at the end of two months A secondary aim is an evaluation of the accuracy and feasibility of GeneXpert performed in a mobile clinic Additional study aims include using chest X-rays obtained during the study to develop and validate of an computer-aided diagnosis CAD software package for TB together with collaborators in the Netherlands as well as establishing whether LAM is detectable at sub-ELISA concentrations in the urine of those with TB
Detailed Description:
Despite recent advances in diagnosis and the availability of effective anti-tuberculous treatment TB remains one of the worlds most devastating infectious disease with a global prevalence of more than 14 million in 2006 In high burden communities with the co-localised HIV epidemic a major problem hampering control efforts and promulgating the TB epidemic is the large reservoir of undiagnosed TB disease This comprises over 50 of the total TB burden HIV-infection with its atypical yet infectious presentation where immunity is attenuated worsens this undetected reservoir Thus there is a large case load in the community that do not access health care or do so late in the course of the disease and there is thus ongoing disease transmission within the community If this caseload in not addressed then the TB epidemic will never be controlled
Intensified case finding seeks to address this problem Intensified case finding is a strategy to identify and treat people with TB who have not sought diagnostic services on their own initiative By contrast passive case finding is only able to identify people with TB presenting to health care facilities In 2008 the WHO and Stop TB partnership identified intensified case-finding as one of four core TB prevention strategies necessary to meet the sixth Millennium Development Goal of halving the prevalence of TB by 2015 To date a number of studies have illustrated the success of intensified case finding to increase case-detection rates especially in HIV-infected populations and to shorten time to diagnosis thereby limiting attendant morbidity and mortality
Given both the importance and resource-intensive nature of intensified case finding it is essential that the optimal operationally feasible and most cost-effective screening strategy be used To date screening strategies have varied widely across studies but all have used a combination of symptom screening radiological CXR and microscopy-centre based laboratory diagnostics smear microscopy and if available and cost permitting TB culture This is a major shortcoming as it is now well established that these standard diagnostic tools perform sub-optimally especially in high HIV prevalent settings With the recent development of a number of novel TB diagnostic tools with superior performance compared to conventional modalities and the potential for point-of-care POC and point-of-treatment usage it is imperative that intensified case-finding strategies be reviewed The 2010 updated WHO Guidelines for intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in resource constrained settings recommends the use of a clinical algorithm for intensified case finding programmes for adults and adolescents living with HIV and it is important that the incremental diagnostic benefit together with the feasibility and cost-effectiveness of these novel TB diagnostic tools be assessed for use in intensified case finding programmes within the context of these updated guidelines
In 2009 Cepheid released the Xpert MTBRIF Assay which is the only system able to deliver answers directly from unprocessed samples by combining on-board preparation of the sample with real-time PCR in less than 2 hours Additionally the Xpert MTBRIF Assay allows for simultaneous on-demand molecular testing for the detection of Mtb and RIF resistance The GeneXpert system consists of a GeneXpert instrument personal computer and disposable fluidic cartridges The system combines cartridge-based sample preparation with amplification and detection in a fully integrated and automated nucleic acid analysis instrument GeneXpert has been shown to be an accurate tool for the rapid diagnosis of tuberculosis in both smear-positive and smear-negative samples with a single Xpert test having a sensitivity of 70 in smear-negative samples A large demonstration study of Gene Xpert based at microscopy-centres is currently underway and preliminary data appear promising However GeneXpert technology has not been used as part of a screening strategy for intensified case finding and its operational feasible as a point-of-treatment diagnostic technology based in a mobile clinic has not yet been assessed
In our recent review we have proposed urinary LAM as a useful rule in test for TB in HIV-infected subjects with advanced immune-suppression Additionally the recent development of a point-of-care urine LAM lateral flow strip test - the Determine TB - with preliminary results suggesting equivalent performance to the LAM ELISA make it an appealing diagnostic for high HIV prevalence areas A recent study has shown urine LAM to be more sensitive than smear-microscopy in an ARV clinic-based TB screening study The use of the Determine TB lateral flow strip test has not been studied as part of an intensified case finding strategy for population-based surveys The Determine TB lateral flow test will be used for screening of HIV-infected patients at point-of-care within the community and subsequent TB clinic referral for sputum-based diagnostics
The XACT study has a randomised control study design to evaluate the impact of a package of novel TB diagnostic tools in the community using a mobile unit compared to standard intensive-case finding methods The feasibility of performing new TB diagnostics at the point-of-care will be examined to determine if the proportion of patients identified initiating and completing TB treatment is greater compared to the standard diagnostic arm Further the cost-effectiveness of TB cases detected and successfully completing treatment between study arms can also be investigated
Intensified case finding seeks to address this problem Intensified case finding is a strategy to identify and treat people with TB who have not sought diagnostic services on their own initiative By contrast passive case finding is only able to identify people with TB presenting to health care facilities In 2008 the WHO and Stop TB partnership identified intensified case-finding as one of four core TB prevention strategies necessary to meet the sixth Millennium Development Goal of halving the prevalence of TB by 2015 To date a number of studies have illustrated the success of intensified case finding to increase case-detection rates especially in HIV-infected populations and to shorten time to diagnosis thereby limiting attendant morbidity and mortality
Given both the importance and resource-intensive nature of intensified case finding it is essential that the optimal operationally feasible and most cost-effective screening strategy be used To date screening strategies have varied widely across studies but all have used a combination of symptom screening radiological CXR and microscopy-centre based laboratory diagnostics smear microscopy and if available and cost permitting TB culture This is a major shortcoming as it is now well established that these standard diagnostic tools perform sub-optimally especially in high HIV prevalent settings With the recent development of a number of novel TB diagnostic tools with superior performance compared to conventional modalities and the potential for point-of-care POC and point-of-treatment usage it is imperative that intensified case-finding strategies be reviewed The 2010 updated WHO Guidelines for intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in resource constrained settings recommends the use of a clinical algorithm for intensified case finding programmes for adults and adolescents living with HIV and it is important that the incremental diagnostic benefit together with the feasibility and cost-effectiveness of these novel TB diagnostic tools be assessed for use in intensified case finding programmes within the context of these updated guidelines
In 2009 Cepheid released the Xpert MTBRIF Assay which is the only system able to deliver answers directly from unprocessed samples by combining on-board preparation of the sample with real-time PCR in less than 2 hours Additionally the Xpert MTBRIF Assay allows for simultaneous on-demand molecular testing for the detection of Mtb and RIF resistance The GeneXpert system consists of a GeneXpert instrument personal computer and disposable fluidic cartridges The system combines cartridge-based sample preparation with amplification and detection in a fully integrated and automated nucleic acid analysis instrument GeneXpert has been shown to be an accurate tool for the rapid diagnosis of tuberculosis in both smear-positive and smear-negative samples with a single Xpert test having a sensitivity of 70 in smear-negative samples A large demonstration study of Gene Xpert based at microscopy-centres is currently underway and preliminary data appear promising However GeneXpert technology has not been used as part of a screening strategy for intensified case finding and its operational feasible as a point-of-treatment diagnostic technology based in a mobile clinic has not yet been assessed
In our recent review we have proposed urinary LAM as a useful rule in test for TB in HIV-infected subjects with advanced immune-suppression Additionally the recent development of a point-of-care urine LAM lateral flow strip test - the Determine TB - with preliminary results suggesting equivalent performance to the LAM ELISA make it an appealing diagnostic for high HIV prevalence areas A recent study has shown urine LAM to be more sensitive than smear-microscopy in an ARV clinic-based TB screening study The use of the Determine TB lateral flow strip test has not been studied as part of an intensified case finding strategy for population-based surveys The Determine TB lateral flow test will be used for screening of HIV-infected patients at point-of-care within the community and subsequent TB clinic referral for sputum-based diagnostics
The XACT study has a randomised control study design to evaluate the impact of a package of novel TB diagnostic tools in the community using a mobile unit compared to standard intensive-case finding methods The feasibility of performing new TB diagnostics at the point-of-care will be examined to determine if the proportion of patients identified initiating and completing TB treatment is greater compared to the standard diagnostic arm Further the cost-effectiveness of TB cases detected and successfully completing treatment between study arms can also be investigated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None