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TuberculosisNCT04240990

Development of a Diagnostic Prediction Score for Tuberculosis in Hospitalized Children With Severe Acute Malnutrition (TB-Speed SAM)

A study testing Development of a score and algorithm for TB treatment decision in hospitalised children with SAM. in people with Tuberculosis and Severe Acute Malnutrition, run by Institut National de la Santé Et de la Recherche Médicale, France at 3 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

TB-Speed SAM is a multicentric, prospective diagnostic cohort study conducted in two countries with high and very high TB incidence (Uganda and Zambia). It aims at assessing several diagnostic tests that could result in the development of a score and algorithm for TB treatment decision in hospitalised children with… Read more about this study

Who is it for?
Ages 2 to 59 months
Conditions the study is for
Tuberculosis, Severe Acute Malnutrition
What is being tested?
Development of a score and algorithm for TB treatment decision in hospitalised children with SAM.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
603 participants
Where
3 sitesin 2 countries
Study dates
4 Nov 2019to 20 Jun 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 2 to 59 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Children aged 2 to 59 months
  • Severe acute malnutrition defined as weight-for-height Z score (WHZ) < -3 standard deviation (SD) or mid-upper arm circumference (MUAC) < 115 mm (in children over 6 months) or clinical signs of bilateral pitting oedema
  • Hospitalized per hospital clinician's decision
  • Parent/guardian informed consent

Who cannot join

  • Ongoing TB treatment or history of intake of anti-TB drugs in the last 3 months

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

Other trials in Zambia

Uganda1 site
  • Mulago National Referral Hospital

    Kampala

Other trials in Uganda

About this study

Official title: Development of a Diagnostic Prediction Score for Tuberculosis in Hospitalized Children With Severe Acute Malnutrition

TB-Speed SAM is a multicentric, prospective diagnostic cohort study conducted in two countries with high and very high TB incidence (Uganda and Zambia). It aims at assessing several diagnostic tests that could result in the development of a score and algorithm for TB treatment decision in hospitalised children with severe acute malnutrition (SAM).

Read the detailed description

There is now strong evidence that undiagnosed and untreated TB increases the risk of death in children, especially those severely malnourished who are highly vulnerable. Specific decision-making tools are therefore urgently needed to guide clinicians from high TB burden and low-income countries to initiate treatment quickly in children with SAM with suspected TB.

A diagnostic prediction score and algorithm was recently proposed by the investigators for TB treatment decision in HIV-infected children with presumptive TB (developed in the ANRS 12229 PAANTHER 01 study). Based on easily collected clinical features, chest X-Ray (CXR), Xpert MTB/RIF, and abdominal ultrasonography, the score aims to help clinicians make a same-day treatment decision. Such a prediction score improving TB diagnosis and shortening time to treatment initiation would be a key benefit in children with SAM.

Based on this experience, the investigators are proposing a diagnostic cohort study enrolling hospitalized severely malnourished children. The study will include the evaluation of several diagnostic tests that could be integrated in the development of a prediction model and subsequent score for the diagnosis of TB in hospitalized children with SAM. This will include Xpert MTB/RIF Ultra performed on one nasopharyngeal aspirate (NPA) and one stool sample, CXR, Quantiferon (QFT) Interferon-Gamma Release Assay (IGRA), Monocyte-to-lymphocyte ratio (MLR), and ultrasonography, which has shown its interest for the diagnosis of TB in both HIV-infected adults and children. In the PAANTHER study, it detected abdominal lymphadenopathy in 50% of culture confirmed TB cases and 35% of all confirmed and unconfirmed cases, with a specificity of 85%.

Using logistic regression, a score will be developed for TB diagnosis, considering confirmed and unconfirmed TB as reference diagnosis, in hospitalized children with SAM. As a secondary objective, and in order to reduce costs, sample collection, and complexity of the diagnostic process, a first-step screening score (excluding Ultra, abdominal ultrasound, and CXR if possible) will be developed to identify children with presumptive TB who would benefit from further diagnostic testing.

Both scores will be internally validated using resampling and will be incorporated in a stepwise algorithm to guide practical implementation of the screening and diagnosis process. The stepwise algorithm will be discussed with local clinicians involved in the study to better adapt it for future use in their routine practice.

The study will be implemented at inpatient nutrition centres from three selected tertiary hospitals in Uganda, and Zambia. A total of 720 children <5 years old with WHO-defined severe acute malnutrition will be enrolled, that is approximately 240 participants per hospital.

Being tested
Development of a score and algorithm for TB treatment decision in hospitalised children with SAM.
Keywords
Tuberculosis, Child, Malnutrition, Diagnosis, Screening
Medical subject headings
Tuberculosis, Severe Acute Malnutrition, Malnutrition, Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Development of a score and algorithm for TB treatment decision in hospitalised children with SAM.Other

    The diagnostic strategy will include an initial clinical, radiographic and bacteriological evaluation of all enrolled children:

    • TB contact history
    • Suggestive TB symptoms in the previous 4 weeks
    • Physical examination
    • Clinical, anthropometric and biochemical assessment of malnutrition
    • Clinical assessment for other non-dietary causes of malnutrition
    • Digitalized CXR
    • Ultra performed on NPA and stool samples, and one gastric aspirate (GA)
    • Mycobacterial culture performed on two GAs
    • Abdominal ultrasonography
    • QuantiFERON®-TB Gold IGRA
    • Monocyte-to-Lymphocyte Ratio (MLR)
    • C-Reactive Protein (CRP)

    TB diagnosis will be made according to national TB guidelines.

Study groups in NCT04240990
Study groupRoleWhat they receive
Prospective cohortExperimentalChildren included in the cohort will all be in the same arm. The patients will benefit from standard-of-care TB diagnosis with additional diagnostic methods.
Receives: Other: Development of a score and algorithm for TB treatment decision in hospitalised children with SAM.

What is being measured

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

  1. Sensitivity of the score obtained

    Sensitivity of the score obtained using predicted probability cut-off with the prediction model for the diagnosis of TB, defined as either confirmed or unconfirmed using the updated Clinical Case Definition for Classification of Intrathoracic Tuberculosis

    Measured: 6 months

  2. Specificity of the score obtained

    Specificity of the score obtained using predicted probability cut-off with the prediction model for the diagnosis of TB

    Measured: 6 months

Secondary outcomes (22)
  1. Prevalence of TB among hospitalized children with SAM

    Proportion of confirmed and unconfirmed TB in the study population

    Measured: 6 months

  2. Clinical characteristics of TB disease in hospitalized children with SAM

    Signs and symptoms of children with tuberculosis (confirmed and unconfirmed)

    Measured: 6 months

  3. Bacteriological characteristics of TB disease in hospitalized children with SAM

    Bacteriological characteristics (mycobacterial culture and drug susceptibility testing) of children with tuberculosis (confirmed and unconfirmed)

    Measured: 6 months

  4. Biological characteristics of TB disease in hospitalized children with SAM

    Haematological and immunological characteristics (full blood count, transaminases, CRP, IFN gamma) of children with tuberculosis (confirmed and unconfirmed)

    Measured: 6 months

  5. Radiological characteristics of TB disease in hospitalized children with SAM

    Radiological features (chest X-ray and abdominal US) of children with tuberculosis (confirmed and unconfirmed)

    Measured: 6 months

  6. Sensitivity of the score obtained

    Sensitivity of the score obtained using predicted probability cut-off with the screening prediction model for the identification of children with presumptive TB requiring further diagnostic evaluation

    Measured: 6 months

  7. Specificity of the score obtained

    Specificity of the score obtained using predicted probability cut-off with the screening prediction model for the identification of children with presumptive TB requiring further diagnostic evaluation

    Measured: 6 months

  8. Estimated time to TB treatment decision in hospitalized children with SAM

    Estimated time to TB treatment decision in hospitalized children with SAM, with and without presumptive TB based on the first-step screening prediction score

    Measured: 6 months

  9. Diagnostic accuracy measures: 1/ Sensitivity of the different tests evaluated for the diagnosis of TB

    Sensitivity of the different tests evaluated for the diagnosis of TB (Ultra performed on NPA and stools, CXR, abdominal ultrasound, QFT, MLR, CRP)

    Measured: 6 months

  10. Diagnostic accuracy measures: 2/ Specificity of the different tests evaluated for the diagnosis of TB

    Specificity of the different tests evaluated for the diagnosis of TB (Ultra performed on NPA and stools, CXR, abdominal ultrasound, QFT, MLR, CRP)

    Measured: 6 months

  11. Diagnostic accuracy measures: 3/ Negative predictive value of the different tests evaluated for the diagnosis of TB

    Negative predictive value of the different tests evaluated for the diagnosis of TB (Ultra performed on NPA and stools, CXR, abdominal ultrasound, QFT, MLR, CRP)

    Measured: 6 months

  12. Diagnostic accuracy measures: 4/ Positive predictive value of the different tests evaluated for the diagnosis of TB

    Positive predictive value of the different tests evaluated for the diagnosis of TB (Ultra performed on NPA and stools, CXR, abdominal ultrasound, QFT, MLR, CRP)

    Measured: 6 months

  13. Diagnostic accuracy measures: 5/ AUROC of diagnostic prediction models with and without the different tests results

    Area Under the Receiver Operating Characteristics curve

    Measured: 6 months

  14. Diagnostic accuracy of Ultra performed on one NPA and one stool sample against a specific microbiological reference standard including Ultra and mycobacterial culture from gastric aspirates

    Proportion of NPAs and stool samples with mycobacterium tuberculosis detected using Ultra

    Measured: 6 months

  15. Proportion of children with NPA and stool samples collected as per study protocol

    Feasibility of NPA and stool samples collection defined as the proportion of children with NPA and stool samples collected as per study protocol

    Measured: 6 months

  16. Proportion of NPA-related adverse events (AEs)

    Safety of NPA collection defined as proportion of AEs (vomiting, nose bleeding, low oxygen saturation, respiratory distress) occurring during NPA

    Measured: 6 months

  17. Tolerability of NPA collection: 1/ Discomfort/pain/distress experienced by the child as assessed by the child

    Discomfort/pain/distress experienced by the child during NPA collection, as assessed by the child using the Wong-Baker face scale (in a subset of children).

    Scale range: 0 (no hurt) - 5 (hurts worst)

    Measured: Within 3 days of inclusion

  18. Tolerability of NPA collection: 2/ Discomfort/pain/distress experienced by the child as assessed by the parents

    Discomfort/pain/distress experienced by the child during NPA collection, as assessed by the parents using the visual analog scale (in a subset of children).

    Scale range: 0 (no pain) - 10 (pain as bad as it could possibly be)

    Measured: Within 3 days of inclusion

  19. Tolerability of NPA collection: 3/ Discomfort/pain/distress experienced by the child as assessed by the nurse

    Discomfort/pain/distress experienced by the child during NPA collection, as assessed by the nurses using the "Face Legs Activity Cry Consolability" behavioral pain scale (in a subset of children).

    Total score range: 0 (relaxed and comfortable) - 10 (severe discomfort/pain). Each item of the FLACC scale - Face, Legs, Activity, Cry, Consolability - has 3 possible quotes: 0 or 1 or 2, with a precise description provided to help with the rating. The total score is obtained by adding individual item scores.

    Measured: Within 3 days of inclusion

  20. Mortality at 6 months

    Mortality at 6 months in children with SAM, with or without TB treatment

    Measured: 6 months

  21. Percentage weight gain 6 months

    Weight gain and WHZ at 6 months in children with SAM, with or without anti-TB treatment

    Measured: 6 months

  22. TB treatment outcomes

    TB treatment outcomes as defined per WHO guidelines (Cured, Treatment completed, Treatment failed, Died, Lost to follow-up, Not evaluated, Treatment success)

    Measured: 6 months

Timeline

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

  1. First posted27 Jan 2020
  2. Study start4 Nov 2019
  3. Primary completion20 Jun 2022
  4. Study completion20 Jun 2022

Resources

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
Not applicable
Intervention model
Single group
Model description
TB-Speed SAM is a multicentric, prospective diagnostic cohort study assessing several diagnostic tests that could result in the development of a score and algorithm for TB treatment decision in hospitalised children with SAM.
Masking
None (open label)
Enrolment
603 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04240990
Sponsor's protocol ID
C18-28
Status last verified
Feb 2025
First submitted
24 Oct 2019
Last updated
10 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Chabala C, Roucher C, Ton Nu Nguyet MH, Babirekere E, Inambao M, Businge G, Kapula C, Shankalala P, Nduna B, Mulenga V, Graham S, Wobudeya E, Bonnet M, Marcy O; TB-Speed SAM study group. Development of tuberculosis treatment decision algorithms in children below 5 years hospitalised with severe acute malnutrition in Zambia and Uganda: a prospective diagnostic cohort study. EClinicalMedicine. 2024 Jun 20;73:102688. doi: 10.1016/j.eclinm.2024.102688. eCollection 2024 Jul.

    PubMed 39007063
  • d'Elbee M, Mafirakureva N, Chabala C, Huyen Ton Nu Nguyet M, Harker M, Roucher C, Businge G, Shankalala P, Nduna B, Mulenga V, Bonnet M, Wobudeya E, Marcy O, Dodd PJ. Treatment decision algorithms for tuberculosis screening and diagnosis in children below 5 years hospitalised with severe acute malnutrition: a cost-effectiveness analysis. EClinicalMedicine. 2025 Apr 19;83:103206. doi: 10.1016/j.eclinm.2025.103206. eCollection 2025 May.

    PubMed 40291345

Questions about this trial

What is this clinical trial studying?

A study testing Development of a score and algorithm for TB treatment decision in hospitalised children with SAM. in people with Tuberculosis and Severe Acute Malnutrition, 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 4 inclusion and 1 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 10 Dec 2025. 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 of the score obtained (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT04240990, which also lists 2 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 10 Dec 2025.

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