TuberculosisNCT04203628
Evaluation of Four Stool Processing Methods Combined With Xpert MTB/RIF Ultra for Diagnosis of Intrathoracic Paediatric TB (TB-Speed - Stool Processing)
A study testing Xpert MTB/Rif Ultra on stool samples and Xpert MTB/Rif Ultra on respiratory sample in people with Tuberculosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 3 sites in 2 countries.
Trial summary
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Read more about this study
- Who is it for?
- Ages Up to 14 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Xpert MTB/Rif Ultra on stool samples and Xpert MTB/Rif Ultra on respiratory sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 215 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 13 Jan 2020to 7 Feb 2022
- 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 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children < 15 years old
- Presumptive intra-thoracic TB based on at least one criterion among the following:
- Persistent cough for more than 2 weeks
- Persistent fever for more than 2 weeks
- Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age < 2)
- Failure of broad-spectrum antibiotics for treatment of pneumonia
Show all 19Show fewer
- Suggestive CXR features
- OR History of contact with a TB case and any of the symptoms listed under point 2 with shorter duration (< 2 weeks) if the child is HIV infected or presents with SAM.
- Signed informed consent by parent or guardian and assent signed by children ≥ 7 years old
- Children < 15 years old
- Presumptive TB based on at least one criterion among the following:
- Persistent cough for more than 2 weeks
- Persistent fever for more than 2 weeks
- Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age < 2)
- Failure of broad-spectrum antibiotics for treatment of pneumonia
- Suggestive CXR features
- OR History of contact with a TB case and any of the symptoms listed under point 2 with shorter duration (< 2 weeks) if the child is HIV infected or presents with SAM.
- One positive Xpert (MTB/Rif or Ultra) result from at least one respiratory sample: sputum, NPA or GA
- Signed informed consent by parent or guardian and assent signed by children ≥ 7 years old
Who cannot join
- > 5 days of antituberculosis treatment in the last 3 months
- History of tuberculosis preventive therapy in the last 3 months
- Confirmed extrapulmonary TB only
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Zambia2 sites
Lusaka University Teaching Hospital
Lusaka
Arthur Davidson Children Hospital
Ndola
About this study
Official title: Evaluation of Four Stool Processing Methods Combined With Xpert MTB/RIF Ultra for Diagnosis of Intrathoracic Paediatric TB
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations. Therefore, in this study, the investigators propose to evaluate the accuracy of different promising stool processing methods in the same population within the same study with an adapted design. Furthermore, no study has so far evaluated for stool testing the new Xpert MTB/RIF Ultra cartridge that has a lower level of detection than the previous Xpert MTB/RIF cartridge. The investigators propose to evaluate the accuracy of Xpert MTB/RIF Ultra (Ultra) performed on stool samples collected from children with presumptive TB and processed using four different processing methods (Standard sucrose flotation method, optimized sucrose flotation method, SPK, and SOS) against bacteriological results from respiratory specimens and to perform a head-to-head comparison of the diagnostic accuracy and feasibility of these different methods in Uganda and Zambia. The selection of processing methods was based on accuracy results, degree of simplification allowing their introduction at PHC level, and finding from the TB-Speed in-vitro stool processing study. The standard sucrose flotation method is kept to assess if results obtained with the optimised sucrose-flotation method in our in-vitro study can be reproduced in-vivo
Read the detailed description
This is a diagnostic study evaluating the diagnostic accuracy of the Ultra assay in stools with a two-stage sequential design starting as a cohort of children with presumptive TB enriched in a second stage with Ultra positive TB cases on respiratory sample. It is both an ancillary to the TB-Speed HIV (C18-27) and the TB-Speed SAM (C18-28) studies and a study enrolling children from routine not enrolled in those two studies.
This design was chosen to be able to evaluate the sensitivity and specificity of the Ultra assay in a smaller sample size that is usually required by a "classical" prospective cohort design and avoiding the bias of overestimation of the sensitivity classically associated with the case-control design. In order to quickly generate data on appropriate stool processing method, and to contribute to the planned WHO recommendations for stool Ultra testing (expected 2nd semester 2020), a two-stage sequential design will be used. Indeed, knowing that on average only 10-15% of children with presumptive TB in a community-based setting will be confirmed, in order to reach the sample size of confirmed cases for the evaluation of sensitivity, 7 to 10 times more children with presumptive TB would need to be enrolled in a prospective design. On the other hand, the number of children with presumptive TB not confirmed with TB for the estimation of the specificity would be reached much earlier. In addition, based on the previous study results, it is known that the specificity of Xpert MTB/RIF assay in stool is high (99% CI:98-99), which would result in a relatively small sample size to evaluate the specificity of the Ultra in stools.
During the first stage, the investigators will offer to join all consecutive presumptive TB cases presenting at study sites to estimate specificity with the expected precision and calculate a preliminary sensitivity estimate. During the second stage, the investigators will keep enrolling only those from TB Speed studies and routine care who are Xpert positive on respiratory samples in order to estimate sensitivity with the expected precision.
This two-stage sequential design first estimating specificity then sensitivity has been described by Wruck et al. as an efficient way of validating diagnostic tests when the prevalence of the disease is low. It would not be feasible to consecutively enrol all children with presumptive TB to describe an expected sensitivity of 60% with 10% precision as this would require over 900 patients, of which, approximately 800 would be culture negative. In the two-stage process described by Wruck, only reference standard positive samples from the original population are selected in stage 2. The investigators adapted this design to the TB context as culture results will only be available after enrollment (and if the child is positive, only after the child has started treatment), hence selecting only those who are Ultra positive on respiratory samples for the second cohort as a way of enriching the study population with a subpopulation that has a higher TB prevalence probability, before their true disease status is confirmed. Other comparable diagnostic studies have either used greater resources to include larger samples sizes or have resorted to reporting imprecise estimates of sensitivity. To our knowledge, this is a relatively unique approach to study design for accuracy studies, with few published examples.
With such design, there should be no bias on the evaluation of the specificity similarly to a classical prospective design because this evaluation will be done among consecutively enrolled children with presumptive TB only. The sensitivity estimates may not be generalizable to all culture confirmed TB children due to the sampling approach. Xpert positive children will be more likely to have higher biological loads, causing a possible inflation of the sensitivity. However, the results will provide valuable information on variations of sensitivities of the different stool processing methods within this population.
An interim analysis will be carried out after the completion of the prospective cohort in order to describe specificity and preliminary results of the sensitivity and the agreement between the processing methods. The recruitment of participants will not be put on hold during the interim analysis. A final analysis will be conducted at the end of the study to describe sensitivity as well as the secondary end points.
- Conditions
- Tuberculosis
- Being tested
- Xpert MTB/Rif Ultra on stool samples, Xpert MTB/Rif Ultra on respiratory sample
- Keywords
- Tuberculosis, Child, Diagnosis, Method, Laboratory
- Medical subject headings
- Tuberculosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xpert MTB/Rif Ultra on stool samplesDiagnostic test
The Xpert MTB/Rif Ultra will be performed on stool samples processed using four different processing methods:
- Standard sucrose flotation method
- Optimized sucrose flotation
- Stool processing kit (SPK)
- Simple One-step method (SOS)
Xpert MTB/Rif Ultra on respiratory sampleDiagnostic test
The Xpert MTB/Rif Ultra will be performed on gastric aspirate or expectorated sputum
| Study group | Role | What they receive |
|---|---|---|
| Prospective cohort | Experimental | Any child with presumptive TB will be proposed to participate in the study.
If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies.
For children identified from the routine practice, the nurse will collect 2 respiratory samples (sputum or GA) in consecutive children with presumptive TB to be tested using Ultra as done in routine care, record symptoms and refer the child for clinical exam and for chest X-ray. For the purpose of the study, 2 stool samples will be collected to be tested with Ultra. In addition, for study purpose the two respiratory samples will be tested with Mycobacterial culture as this test is not routinely prescribed for TB diagnosis in the study sites Receives: Diagnostic Test: Xpert MTB/Rif Ultra on stool samples; Diagnostic Test: Xpert MTB/Rif Ultra on respiratory sample |
| Enrichment cohort | Experimental | Any child with presumptive TB and a positive Xpert result from one respiratory sample (NPA, IS or GA) will be proposed to participate in the study.
If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies
For children identified from the routine care, once enrolled, samples collected as routine practice will be tested with mycobacterial culture in addition to Xpert. If needed an additional respiratory sample will be collected (sputum or GA) and tested with Mycobacterial culture. The nurse will also record symptoms, refer the child for clinical exam and for chest Xray, and collect stool samples. HIV-testing will be offered for children with unknown HIV-status Receives: Diagnostic Test: Xpert MTB/Rif Ultra on stool samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity and sensibility of Ultra on stool
Sensitivity and specificity of Ultra on stool using TB culture reference standard (LJ and MGIT) in two respiratory samples (two sputums or two gastric aspirates according the age of the child).
Measured: 8 weeks
Secondary outcomes (11)
Per-protocol analysis of diagnostic accuracy of Ultra on stool using TB culture reference standard
Per-protocol analysis of sensitivities and specificities of Ultra on stool using TB culture reference standard (LJ ans MGIT) in respiratory sample, excluding invalid Ultra results and contaminated culture results from analysis.
Measured: 8 weeks
Head-to-head comparisons
Measured: 8 weeks
Sensitivities and specificities of each sampling method
- Sensitivities and specificities of each sampling method using TB culture reference standard
- Sensitivities and specificities of each sampling method using the TB composite reference standard as defined by the Expert Committee (Clinical Case Definition for Classification of Intrathoracic Tuberculosis in Children)
Measured: 8 weeks
Proportion of Ultra "trace" results in stools out of the number of stools tested with Ultra
Measured: 8 weeks
Proportion of Ultra semi-quantitative results "very low"; "low"; "medium" and "high" in stool
Measured: 8 weeks
Proportion of invalid Ultra results from stool out of the number of stools tested with Ultra
Measured: 8 weeks
Proportion of Rifampicin resistant results on Ultra (stool and respiratory), LPA and DST
Measured: 8 weeks
Stratification of characteristics and laboratory results by age groups (≤2 years and > 2 years)
Measured: 8 weeks
Proportion of children successfully providing a stool sample
Measured: 8 weeks
Relative gain of the 2nd stool sample as compared to the 1st one
Relative gain of the 2nd stool sample as compared to the 1st one as measured by the number of additional positive results obtained from the addition of the 2nd sample as compared to the results of the first sample only
Measured: 8 weeks
Feasibility assessment of the stool processing methods
Feasibility assessment by laboratory technician of their perception of ease of use, safety and suitability to low primary health care setting using a questionnaire and a standard "Ease of use score".
The assessment will be divided into 2 parts:
- General characteristics of the stool processing method will be scored according to a rating system laying on 10 criteria describing the ease of use. The score range from 1 to 50, each criteria being scored from 1 to 5. A low score reflects the lowest levels of complexity of sample processing procedures.
- Characteristic related to the opinion of the laboratory technician (rapidity and ease of performance, quality of instruction sheet, perceived feasibility at each step). The opinion of all study laboratory technicians will be assessed independently and using a short self-administered questionnaire containing open and multiple-choice questions
Measured: 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start13 Jan 2020
- Primary completion7 Feb 2022
- Study completion7 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Enrolment will have 2 stages. During stage 1 (prospective cohort stage), all consecutive children with presumptive TB enrolled in the TB-Speed HIV or TB-Speed SAM or seen in routine care if ineligible for those two studies will be proposed to participate in the study until we reach the number needed for the evaluation of specificity. All children with presumptive TB will have at least two respiratory samples collected (ES or GA) tested with Ultra and mycobacterial culture. The cohort will be closed once the sample size of presumptive TB children with two negative Ultra results from respiratory samples will be reached. During the 2nd phase (enrichment phase), only children with presumptive TB who are Xpert positive on at least one respiratory sample will be proposed to participate in the study in order to complement the number of confirmed TB cases required for the evaluation of the sensitivity.
- Masking
- None (open label)
- Enrolment
- 215 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- UNITAID
- Responsible party
- Sponsor
- Investigators
- Maryline Bonnet, MD, PhD, Principal investigator, Institut de Recherche pour le Développement (IRD) Montpellier, FranceOlivier Marcy, MD, PhD, Principal investigator, University of Bordeaux, FranceEric Wobudeya, MD, PhD, Principal investigator, MU-JHU Care Ltd, Kampala, Uganda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04203628
- Sponsor's protocol ID
- C19-34
- Status last verified
- May 2024
- First submitted
- 16 Dec 2019
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will be available after de-identification
Publications
Lounnas M, Masama EN, Beneteau S, Kasakwa K, Kaitano R, Nabeta P, Ruhwald M, De Haas P, Tiemersma EW, Nduna B, Nicol MP, Eyangoh S, Wobudeya E, Mwanga-Amumpaire J, Chabala C, Marcy O, Bonnet M; TB-Speed Stool Study Group. Centrifuge-free stool processing methods for Xpert MTB/RIF Ultra tuberculosis diagnosis in children in Uganda and Zambia: an observational, prospective, diagnostic accuracy study. Lancet Microbe. 2025 Aug;6(8):101055. doi: 10.1016/j.lanmic.2024.101055. Epub 2025 Jun 23.
PubMed 40570871
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Four Stool Processing Methods Combined With Xpert MTB/RIF Ultra for Diagnosis of Intrathoracic Paediatric TB
- ClinicalTrials.gov ID
- NCT04203628
- Acronym / sponsor ID
- C19-34
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Child, Diagnosis, Method, Laboratory
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- UNITAID
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 7 Feb 2022 (actual)
- Study completion
- 7 Feb 2022 (actual)
- First posted
- 18 Dec 2019 (actual)
- 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.
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations. Therefore, in this study, the investigators propose to evaluate the accuracy of different promising stool processing methods in the same population within the same study with an adapted design. Furthermore, no study has so far evaluated for stool testing the new Xpert MTB/RIF Ultra cartridge that has a lower level of detection than the previous Xpert MTB/RIF cartridge. The investigators propose to evaluate the accuracy of Xpert MTB/RIF Ultra (Ultra) performed on stool samples collected from children with presumptive TB and processed using four different processing methods (Standard sucrose flotation method, optimized sucrose flotation method, SPK, and SOS) against bacteriological results from respiratory specimens and to perform a head-to-head comparison of the diagnostic accuracy and feasibility of these different methods in Uganda and Zambia. The selection of processing methods was based on accuracy results, degree of simplification allowing their introduction at PHC level, and finding from the TB-Speed in-vitro stool processing study. The standard sucrose flotation method is kept to assess if results obtained with the optimised sucrose-flotation method in our in-vitro study can be reproduced in-vivo
Detailed description
This is a diagnostic study evaluating the diagnostic accuracy of the Ultra assay in stools with a two-stage sequential design starting as a cohort of children with presumptive TB enriched in a second stage with Ultra positive TB cases on respiratory sample. It is both an ancillary to the TB-Speed HIV (C18-27) and the TB-Speed SAM (C18-28) studies and a study enrolling children from routine not enrolled in those two studies.
This design was chosen to be able to evaluate the sensitivity and specificity of the Ultra assay in a smaller sample size that is usually required by a "classical" prospective cohort design and avoiding the bias of overestimation of the sensitivity classically associated with the case-control design. In order to quickly generate data on appropriate stool processing method, and to contribute to the planned WHO recommendations for stool Ultra testing (expected 2nd semester 2020), a two-stage sequential design will be used. Indeed, knowing that on average only 10-15% of children with presumptive TB in a community-based setting will be confirmed, in order to reach the sample size of confirmed cases for the evaluation of sensitivity, 7 to 10 times more children with presumptive TB would need to be enrolled in a prospective design. On the other hand, the number of children with presumptive TB not confirmed with TB for the estimation of the specificity would be reached much earlier. In addition, based on the previous study results, it is known that the specificity of Xpert MTB/RIF assay in stool is high (99% CI:98-99), which would result in a relatively small sample size to evaluate the specificity of the Ultra in stools.
During the first stage, the investigators will offer to join all consecutive presumptive TB cases presenting at study sites to estimate specificity with the expected precision and calculate a preliminary sensitivity estimate. During the second stage, the investigators will keep enrolling only those from TB Speed studies and routine care who are Xpert positive on respiratory samples in order to estimate sensitivity with the expected precision.
This two-stage sequential design first estimating specificity then sensitivity has been described by Wruck et al. as an efficient way of validating diagnostic tests when the prevalence of the disease is low. It would not be feasible to consecutively enrol all children with presumptive TB to describe an expected sensitivity of 60% with 10% precision as this would require over 900 patients, of which, approximately 800 would be culture negative. In the two-stage process described by Wruck, only reference standard positive samples from the original population are selected in stage 2. The investigators adapted this design to the TB context as culture results will only be available after enrollment (and if the child is positive, only after the child has started treatment), hence selecting only those who are Ultra positive on respiratory samples for the second cohort as a way of enriching the study population with a subpopulation that has a higher TB prevalence probability, before their true disease status is confirmed. Other comparable diagnostic studies have either used greater resources to include larger samples sizes or have resorted to reporting imprecise estimates of sensitivity. To our knowledge, this is a relatively unique approach to study design for accuracy studies, with few published examples.
With such design, there should be no bias on the evaluation of the specificity similarly to a classical prospective design because this evaluation will be done among consecutively enrolled children with presumptive TB only. The sensitivity estimates may not be generalizable to all culture confirmed TB children due to the sampling approach. Xpert positive children will be more likely to have higher biological loads, causing a possible inflation of the sensitivity. However, the results will provide valuable information on variations of sensitivities of the different stool processing methods within this population.
An interim analysis will be carried out after the completion of the prospective cohort in order to describe specificity and preliminary results of the sensitivity and the agreement between the processing methods. The recruitment of participants will not be put on hold during the interim analysis. A final analysis will be conducted at the end of the study to describe sensitivity as well as the secondary end points.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Enrolment will have 2 stages. During stage 1 (prospective cohort stage), all consecutive children with presumptive TB enrolled in the TB-Speed HIV or TB-Speed SAM or seen in routine care if ineligible for those two studies will be proposed to participate in the study until we reach the number needed for the evaluation of specificity. All children with presumptive TB will have at least two respiratory samples collected (ES or GA) tested with Ultra and mycobacterial culture. The cohort will be closed once the sample size of presumptive TB children with two negative Ultra results from respiratory samples will be reached. During the 2nd phase (enrichment phase), only children with presumptive TB who are Xpert positive on at least one respiratory sample will be proposed to participate in the study in order to complement the number of confirmed TB cases required for the evaluation of the sensitivity.
| Arm | Type | Receives |
|---|---|---|
| Prospective cohort | Experimental | Diagnostic Test: Xpert MTB/Rif Ultra on stool samples, Diagnostic Test: Xpert MTB/Rif Ultra on respiratory sampleAny child with presumptive TB will be proposed to participate in the study. If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies. For children identified from the routine practice, the nurse will collect 2 respiratory samples (sputum or GA) in consecutive children with presumptive TB to be tested using Ultra as done in routine care, record symptoms and refer the child for clinical exam and for chest X-ray. For the purpose of the study, 2 stool samples will be collected to be tested with Ultra. In addition, for study purpose the two respiratory samples will be tested with Mycobacterial culture as this test is not routinely prescribed for TB diagnosis in the study sites |
| Enrichment cohort | Experimental | Diagnostic Test: Xpert MTB/Rif Ultra on stool samplesAny child with presumptive TB and a positive Xpert result from one respiratory sample (NPA, IS or GA) will be proposed to participate in the study. If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies For children identified from the routine care, once enrolled, samples collected as routine practice will be tested with mycobacterial culture in addition to Xpert. If needed an additional respiratory sample will be collected (sputum or GA) and tested with Mycobacterial culture. The nurse will also record symptoms, refer the child for clinical exam and for chest Xray, and collect stool samples. HIV-testing will be offered for children with unknown HIV-status |
Who may qualify
- Ages
- Up to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- Children < 15 years old
- Presumptive intra-thoracic TB based on at least one criterion among the following:
- OR History of contact with a TB case and any of the symptoms listed under point 2 with shorter duration (< 2 weeks) if the child is HIV infected or presents with SAM.
- Signed informed consent by parent or guardian and assent signed by children ≥ 7 years old
- Children < 15 years old
Key exclusion criteria (3 listed)
- > 5 days of antituberculosis treatment in the last 3 months
- History of tuberculosis preventive therapy in the last 3 months
- Confirmed extrapulmonary TB only
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 Ultra on stool samplesThe Xpert MTB/Rif Ultra will be performed on stool samples processed using four different processing methods: * Standard sucrose flotation method * Optimized sucrose flotation * Stool processing kit (SPK) * Simple One-step method (SOS) | Diagnostic test | Enrichment cohort, Prospective cohort |
| Xpert MTB/Rif Ultra on respiratory sampleThe Xpert MTB/Rif Ultra will be performed on gastric aspirate or expectorated sputum | Diagnostic test | Prospective cohort |
Primary outcome
Sensitivity and sensibility of Ultra on stool
Time frame: 8 weeks
Sensitivity and specificity of Ultra on stool using TB culture reference standard (LJ and MGIT) in two respiratory samples (two sputums or two gastric aspirates according the age of the child).
11 secondary outcomes
Per-protocol analysis of diagnostic accuracy of Ultra on stool using TB culture reference standard
Time frame: 8 weeks
Head-to-head comparisons
Time frame: 8 weeks
Sensitivities and specificities of each sampling method
Time frame: 8 weeks
Proportion of Ultra "trace" results in stools out of the number of stools tested with Ultra
Time frame: 8 weeks
Proportion of Ultra semi-quantitative results "very low"; "low"; "medium" and "high" in stool
Time frame: 8 weeks
Proportion of invalid Ultra results from stool out of the number of stools tested with Ultra
Time frame: 8 weeks
Proportion of Rifampicin resistant results on Ultra (stool and respiratory), LPA and DST
Time frame: 8 weeks
Stratification of characteristics and laboratory results by age groups (≤2 years and > 2 years)
Time frame: 8 weeks
Proportion of children successfully providing a stool sample
Time frame: 8 weeks
Relative gain of the 2nd stool sample as compared to the 1st one
Time frame: 8 weeks
Feasibility assessment of the stool processing methods
Time frame: 25 months
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 16 May 2024.
- Derived from this study: PubMed 40570871Lounnas M, Masama EN, Beneteau S, Kasakwa K, Kaitano R, Nabeta P, Ruhwald M, De Haas P, Tiemersma EW, Nduna B, Nicol MP, Eyangoh S, Wobudeya E, Mwanga-Amumpaire J, Chabala C, Marcy O, Bonnet M; TB-Speed Stool Study Group. Centrifuge-free stool processing methods for Xpert MTB/RIF Ultra tuberculosis diagnosis in children in Uganda and Zambia: an observational, prospective, diagnostic accuracy study. Lancet Microbe. 2025 Aug;6(8):101055. doi: 10.1016/j.lanmic.2024.101055. Epub 2025 Jun 23.
- TB-Speed project official websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data will be available after de-identification
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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.
Maryline Bonnet, MD, PhD principal investigator
Institut de Recherche pour le Développement (IRD) Montpellier, France
Olivier Marcy, MD, PhD principal investigator
University of Bordeaux, France
Eric Wobudeya, MD, PhD principal investigator
MU-JHU Care Ltd, Kampala, Uganda
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Xpert MTB/Rif Ultra on stool samples and Xpert MTB/Rif Ultra on respiratory sample in people with Tuberculosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 3 sites in 2 countries.
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 19 inclusion and 3 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 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Zambia, Uganda. 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?
Sensitivity and sensibility of Ultra on stool (time frame: 8 weeks). 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 NCT04203628, which also lists 1 linked publication.
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 16 May 2024.