Evaluating a New Stool Based qPCR for Diagnosis of Tuberculosis in Children and People Living With HIV (Stool4TB)
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|ClinicalTrials.gov Identifier: NCT05047315|
Recruitment Status : Not yet recruiting
First Posted : September 17, 2021
Last Update Posted : September 17, 2021
|Condition or disease|
|Tuberculosis Diagnoses Disease|
Tuberculosis (TB) continues to be a leading cause of morbidity and mortality among children and people living with HIV (PLHIV). Despite significant progress in TB diagnostics, improvement of childhood TB diagnosis continues to be a major challenge and is a key pillar of the WHO "End TB Strategy". TB laboratory confirmation is particularly challenging in children and PLHIV given the difficulty in obtaining sputum samples, and the pauci-bacillary nature of disease. In consequence, bacteriological confirmation of pulmonary TB in young children and immunosuppressed PLHIV remains disappointingly low. Inability to bacteriologically confirm TB, results in both i) under diagnosis which leads to worse outcomes including increased mortality and ii) over or under diagnosis, and poor resource allocation. Given the limitations of currently available sputum-based diagnostic tests in these vulnerable populations, there is a need to develop new tools and identify easy to collect non-respiratory specimens which, combined, could improve bacteriological confirmation. Preliminary data suggest that a new platform, an innovative stool homogenization and DNA isolation method, adds value to existing sputum-based diagnostics by increasing the rates of bacteriological confirmation, and could also be useful as a monitoring tool for treatment response. This platform has the potential to be adapted to a point of care (POC) diagnostic and thus easily implemented in resource-constrained basic health care centres.
Objective: The aim of this project is to evaluate the diagnostic performance of the stool bead-based real-time quantitative PCR (qPCR) platform for TB diagnosis in children and PLHIV. This will be evaluated in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the large TB case detection gap by improving TB confirmation rates in children and PLHIV, while proving feasible and acceptable.
• Evaluate the diagnostic accuracy of a stool-based real-time quantitative PCR for detecting DNA of Mycobacterium tuberculosis (MTB qPCR), compared to a composite reference standard (sputum and stool Xpert Ultra, sputum culture and urine TB-LAM).
- Evaluate the diagnostic accuracy of the stool-based Mtb qPCR to individual sputum and stool Xpert Ultra, urine LAM, sputum smear and sputum culture (MGIT) results using a consensus clinical case definition as the reference standard.
- Evaluate the usefulness of the quantitative stool-based MTB qPCR platform as a tool to monitor treatment response for children and PLHIV.
- To create a biorepository of well characterized pediatric samples at each of the study sites to support the future development and evaluation of novel biomarker research.
Methodology: This is a prospective diagnostic evaluation study with a nested longitudinal cohort evaluation. During a 30-month recruitment period, people with presumptive TB will consecutively enroll being part of two study groups: Children less than 8 years of age, irrespective of HIV status (N=1295) and adults living with HIV, irrespective of immunological status (N=650). Sixty extra people will take part as healthy (asymptomatic) controls. After clinical, radiological and bacteriological evaluation, TB cases will be treated according to national guidelines. Participants diagnosed with TB will be followed up for 6 months since treatment initiation in order to assess treatment response and outcomes. A clinical case definition will be established as a reference standard and defined as any participant in whom a decision is made to start ATT (TB cases will be classified as confirmed or unconfirmed). Specifically, children will be classified into 3 distinct pediatric endpoint categories (confirmed TB, unconfirmed TB and Unlikely TB) based on bacteriological, radiological and clinical criteria, following international consensus guidelines.
|Study Type :||Observational|
|Estimated Enrollment :||1945 participants|
|Official Title:||Evaluating a New Stool Based qPCR for Diagnosis of Tuberculosis in Children and People Living With HIV|
|Estimated Study Start Date :||October 1, 2021|
|Estimated Primary Completion Date :||June 1, 2023|
|Estimated Study Completion Date :||October 1, 2024|
- Diagnostic performance qPCR test in stool samples [ Time Frame: 2 months ]
Diagnostic performance (Sensitivity, specificity, negative and positive predictive value) of the qPCR test in stool samples with respect to:
- bacteriologically confirmed tuberculosis as a composite gold standard of any of the other tests positive (including induced sputum and gastric aspirate Xpert Ultra and MGIT culture, stool Ultra or TB-LAM in urine)
- clinical reference standard case definition (S. Graham et al.; CID 2015).
- comparison of dignostic performance [ Time Frame: 2 months ]
Diagnostic performance of the qPCR test in stool compared to each of the other microbiological confirmation tests separately with respect to:
A) bacteriologically confirmed tuberculosis as a composite excluding index/comparator).
B) clinical l reference standard case definition (S. Graham et al.; CID 2015).
- monitor response to TB treatment [ Time Frame: 6 months ]Ability of qPCR test in stool to monitor response to TB treatment, by comparing the change in readout over time while receiving TB treatment to that of Xpert Ultra in sputum and in stool.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05047315
|Centro de investigação de Saúde de Manhiça|
|Manhiça, Maputo, Mozambique, 1929|
|Contact: Sozinho Acacio email@example.com|
|Baylor Eswatini Clinical Centre of Excellence (COE)|
|Contact: Alexander Kay alexander.Kay@bcm.edu|
|Contact: Willy Ssengooba firstname.lastname@example.org|
|Principal Investigator:||Alberto L García-Basteiro, MD, PhD||Barcelona Institute for Global Health|
|Study Director:||Elisa López Varela, MD, PhD||Barcelona Institute for Global Health|