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TuberculosisNCT06239337

Evaluation of Xpert MTB/RIF Ultra in Stools and Urine to Improve Tuberculosis Diagnosis in Children

An observational study of Tuberculosis and Pediatric Infectious Disease, run by Medecins Sans Frontieres, Spain at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Tuberculosis (TB) diagnosis in children is challenging in low and middle-income countries where access to TB culture and X-ray is limited. More than half cases of childhood TB remain undiagnosed every year. A delay in TB diagnosis can lead to an increase in preventable morbidity and mortality. Read more about this study

Who is it for?
Ages 6 months to 15 years
Conditions the study is for
Tuberculosis, Pediatric Infectious Disease
What is being tested?
Xpert MTB/RIF Ultra in stools and urine
How many people
563 participants
Where
2 sitesin 2 countries
Study dates
26 Jun 2019to 15 Dec 2023
How long will I take part?
7 Days
Phase
Observational
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 6 months to 15 years
  • All sexes
  • Child

Study population: The research population are children with presumptive TB at Malakal hospitals (South Sudan) at Simão Mendes National Hospital (Guinea-Bissau).

Who may be able to join

  • Any child from 6 months of life to 15 years old
  • TB suspected according to diagnostic criteria
  • Informed consent provided by legal responsible or companion

Who cannot join

  • Patients who have received TB treatment for > 1 day in the last 3 months
  • Patients not producing stools or urine during period of admission and prior to starting TB drugs

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Guinea-Bissau1 site
  • Simao Mendes hospital

    Bissau

Other trials in Guinea-Bissau

South Sudan1 site
  • Malakal hospital

    Malakal, Upper Nile

About this study

Tuberculosis (TB) diagnosis in children is challenging in low and middle-income countries where access to TB culture and X-ray is limited. More than half cases of childhood TB remain undiagnosed every year. A delay in TB diagnosis can lead to an increase in preventable morbidity and mortality.

This study aims to provide evidence on the diagnostic accuracy of Xpert MTB/RIF Ultra in stools and urine for TB diagnosis in children.

Read the detailed description

This multicentric cross-sectional study took place at Malakal hospitals from November 2019 to December 2023, and at Simão Mendes National Hospital between July 2019 and April 2020. Children with presumptive TB underwent clinical and laboratory evaluation.

Study Population, Clinical, and Laboratory procedures Children 6 months to 15 years were considered presumptive TB cases if they showed persistent cough for more than 2 weeks, unexplained fever for more than 1 week or signs of extrapulmonary TB such as: gibbous deformity of the spine, lymphadenopathy, subacute meningitis, distended abdomen with ascites, diarrhoea for more than two weeks, painless enlarged joints, or pleural effusion.

Presumptive TB cases were also identified after a week of inpatient admission, characterized by low weight gain despite nutritional treatment, persistent pneumonia or cough despite adequate antibiotic therapy, persistent fever (>38ºC), and persistent or aggravated fatigue. Patients were screened for TB based on their medical history and clinical presentation, including TB contacts, past TB treatment or known HIV infection; physical examination was conducted in all patients and included relevant anthropometrics (Mid-Upper-Arm Circumference (MUAC), Weight-for-height z scores (WHZ) and/or body mass index (BMI) for age z scores). All patients with unknown HIV status were tested for HIV and were tested for at least one pulmonary or extrapulmonary sample (considered as gold standard), and one stool and one urine samples.

All patients underwent a diagnostic evaluation and were included in three different categories: Confirmed TB (patients who had an Xpert MTB/RIF Ultra positive in one of the samples); Unconfirmed TB (clinical TB diagnosis without microbiological confirmation); Unlikely TB (alternative diagnosis with adequate response to alternative treatments, and TB treatment not started).

Respiratory samples included naso-pharyngeal aspirate, gastric lavage, or spontaneous sputum; extrapulmonary samples included lymph node puncture, pus aspirate, and ascetic, pleural, or cerebrospinal fluids. Stools and urine were collected from all patients as well. All specimens were kept between 2 and 8ºC until processed, which was done within 24 hours. Xpert MTB/RIF Ultra was performed in all collected sample.

In Malakal, MSF supported the TB program in collaboration with the Ministry of Health (MoH) all along the study. In Bissau, all results were communicated to MoH who were responsible for treatment initiation.

Being tested
Xpert MTB/RIF Ultra in stools and urine
Keywords
Pediatric TB, Xpert MTB/RIF Ultra, Stools, Urine
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 Ultra in stools and urineDiagnostic test

    All children with presumptive TB had at least 1 sample collected of respiratory or extrapulmonary specimen (considered as gold standard) and 1 sample of stools and 1 sample of urine. All of them were analyzed with Xpert MTB/RIF Ultra.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in presumptive TB pediatric cases in comparison to Xpert MTB/RIF Ultra in respiratory/extrapulmonary sample

    To determine the sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in presumptive TB pediatric cases in comparison to Xpert MTB/RIF Ultra in respiratory/extrapulmonary sample

    Measured: Through study completion, up to 60 months

Secondary outcomes (2)
  1. To determine sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in subpopulations: HIV/not HIV, SAM/no SAM, <5 years old vs. 5 or more years old.

    To determine sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in subpopulations: HIV/not HIV, SAM/no SAM, <5 years old vs. 5 or more years old.

    Measured: Through study completion, up to 60 months

  2. To determine the added diagnostic yield of Xpert MTB/RIF Ultra in stool and urine samples when gold standard is negative

    To determine the added diagnostic yield of Xpert MTB/RIF Ultra in stool and urine samples when gold standard is negative

    Measured: Through study completion, up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2024
  2. Study start26 Jun 2019
  3. Primary completion1 Jun 2023
  4. Study completion15 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Cross-sectional
Enrolment
563 participants (actual)
Target duration
7 Days
IDs, dates and publications
ClinicalTrials.gov ID
NCT06239337
Sponsor's protocol ID
MSF18115
Status last verified
Jan 2024
First submitted
15 Jan 2024
Last updated
2 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: This study will follow MSF data protection policy and IPD will be shared under request to Medical Director.

Publications

  • Jenkins HE, Yuen CM, Rodriguez CA, Nathavitharana RR, McLaughlin MM, Donald P, Marais BJ, Becerra MC. Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2017 Mar;17(3):285-295. doi: 10.1016/S1473-3099(16)30474-1. Epub 2016 Dec 8.

    PubMed 27964822
  • POSEE Info Note_Pediatric TB diagnosis_Final_17.6.2021.pdf. Taskforce PTOaSEEP. Summary guidance for Microbiological and Clinical Diagnosis of pulmonary tuberculosis among Children: Pediatric TB Operational and Sustainability Expertise Exchange (POSEE) Taskforce, 2021.

  • Dodd PJ, Prendergast AJ, Beecroft C, Kampmann B, Seddon JA. The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis. Thorax. 2017 Jun;72(6):559-575. doi: 10.1136/thoraxjnl-2016-209421. Epub 2017 Jan 23.

    PubMed 28115682
  • WHO consolidated guidelines on tuberculosis: Module 5: Management of tuberculosis in children and adolescents [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK579387/

    PubMed 35404556
  • Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, Gonzalez Fernandez L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y. Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children. Cochrane Database Syst Rev. 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3.

    PubMed 36065889
  • Atherton RR, Cresswell FV, Ellis J, Kitaka SB, Boulware DR. Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary. Front Pediatr. 2019 Feb 28;7:34. doi: 10.3389/fped.2019.00034. eCollection 2019.

    PubMed 30873392
  • Vessiere A, Font H, Gabillard D, Adonis-Koffi L, Borand L, Chabala C, Khosa C, Mavale S, Moh R, Mulenga V, Mwanga-Amumpere J, Taguebue JV, Eang MT, Delacourt C, Seddon JA, Lounnas M, Godreuil S, Wobudeya E, Bonnet M, Marcy O. Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial. BMC Pediatr. 2021 Mar 20;21(1):136. doi: 10.1186/s12887-021-02576-5.

    PubMed 33743621
  • Kabir S, Rahman SMM, Ahmed S, Islam MS, Banu RS, Shewade HD, Thekkur P, Anwar S, Banu NA, Nasrin R, Uddin MKM, Choudhury S, Ahmed S, Paul KK, Khatun R, Chisti MJ, Banu S. Xpert Ultra Assay on Stool to Diagnose Pulmonary Tuberculosis in Children. Clin Infect Dis. 2021 Jul 15;73(2):226-234. doi: 10.1093/cid/ciaa583.

    PubMed 32421765
  • Sun L, Liu Y, Fang M, Chen Y, Zhu Y, Xia C, Jia J, Quan S, Wang Y, Tian X, Shi Y, Duan L, Shi X, Liao Q, Wan C, Shen A. Use of Xpert MTB/RIF Ultra assay on stool and gastric aspirate samples to diagnose pulmonary tuberculosis in children in a high-tuberculosis-burden but resource-limited area of China. Int J Infect Dis. 2022 Jan;114:236-243. doi: 10.1016/j.ijid.2021.11.012. Epub 2021 Nov 10.

    PubMed 34774781
  • Moreto-Planas L, Mahajan R, Fidelle Nyikayo L, Ajack YBP, Tut Chol B, Osman E, Sangma M, Tobi A, Gallo J, Biague E, Goncalves R, Rocaspana M, Medina C, Camara M, Flevaud L, Ruby LC, Belard S, Sagrado MJ, Molina I, Llosa AE. Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Medecins Sans Frontieres Experience in Guinea-Bissau and South Sudan. Open Forum Infect Dis. 2024 May 2;11(5):ofae221. doi: 10.1093/ofid/ofae221. eCollection 2024 May.

    PubMed 38798893

Questions about this trial

What is this clinical trial studying?

An observational study of Tuberculosis and Pediatric Infectious Disease, run by Medecins Sans Frontieres, Spain at 2 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 3 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 2 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Guinea-Bissau, South Sudan. 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?

To determine the sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in presumptive TB pediatric cases in comparison to Xpert MTB/RIF Ultra in respiratory/extrapulmonary sample (time frame: Through study completion, up to 60 months). 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 NCT06239337, which also lists 10 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 2 Feb 2024.

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