AzTrials
AzTrials

TuberculosisNCT05526885

Tuberculosis Diagnostic Trial of CAD4TB Screening Alone Compared to CAD4TB Screening Combined With a CRP Triage Test, Both Followed by Confirmatory Xpert MTB/RIF Ultra in Communities of Lesotho and South Africa

A study testing CAD4TB, POC-CRP and Xpert MTB/RIF Ultra in people with Tuberculosis, run by Klaus Reither 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

According to WHO, about 40% of the incident TB cases in 2020 are either under-reported or under-diagnosed causing on one hand major health risks and on the other hand catastrophic financial consequences. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Tuberculosis
What is being tested?
CAD4TB, POC-CRP and Xpert MTB/RIF Ultra
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20,000 participants
Where
2 sitesin 2 countries
Study dates
7 Sep 2022to 31 Dec 2024
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 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any study-related procedure
  • Adults (≥18 years)

Who cannot join

  • Any condition for which participation in the study, as judged by the investigator or a designated staff member, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
  • Seriously ill person who needs immediate medical care
  • Current anti-TB treatment (preventive TB treatment permitted)
  • Lesotho only: Pregnancy (self-reported)

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Lesotho1 site

  • SolidarMed

    Maseru

Other trials in Lesotho

South Africa1 site

  • Human Sciences Research Council

    Pietermaritzburg, KwaZulu-Natal

Other trials in South Africa

About this study

According to WHO, about 40% of the incident TB cases in 2020 are either under-reported or under-diagnosed causing on one hand major health risks and on the other hand catastrophic financial consequences. In particular, indigent people in hard-to-reach communities with high TB/HIV burden are at high risk of missed or delayed diagnoses. Hence, active case finding for TB remains an integral part of tuberculosis control in high-risk groups, such as people living with HIV (PLHIV) or diabetes mellitus, people living in specific geographical locations associated with a high burden of TB and poor access to health care, miners, or prisoners. CAD4TB (Delft Imaging, NL), a digital chest X-ray analysis software, and point-of care C-reactive protein assay (POC-CRP; e.g. LumiraDx, UK), which detects a cytokine induced acute phase protein, are two tests which have great potential of becoming a screening and triage test for TB as outlined in the WHO target product profiles. Data on CAD4TB and CRP suggest that accuracy can be improved if thresholds are stratified by patient characteristics, such as HIV status, history of TB and TB symptoms. TB TRIAGE+ Trial takes place in the communities of Lesotho and South Africa, which present high prevalence of subclinical TB, where a symptom-based screening would miss almost half of all infectious TB cases. TB TRIAGE+ Trials conducts a direct (in the same individual) comparison of the two screening/triaging approaches which are not based on symptoms: CAD4TB screening alone (approach 1) versus CAD4TB screening with POC-CRP triage testing (approach 2), and followed by confirmatory Xpert MTB/RIF Ultra testing in both approaches. TB TRIAGE TRIAL is investigates the hypothesis that a community-based active case finding strategy with CAD4TB screening with POC-CRP triage testing (approach 2) will be non-inferior compared to CAD4TB screening alone (approach 1) with regard to yield of detected TB cases and superior with regard to cost effectiveness.

Conditions
Tuberculosis
Being tested
CAD4TB, POC-CRP, Xpert MTB/RIF Ultra
Keywords
Lesotho, South Africa, community-based, tuberculosis, active case findings, cost-effectiveness, CAD4TB, POC-CRP, Xpert MTB/RIF Ultra, triage, screening
Medical subject headings
Tuberculosis

What participants receive

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

  • CAD4TBDiagnostic test

    A posterior anterior digital chest X-ray incoporated in a mobile diagnostic unit is analysed by CAD4TB version 7 (Delft Imaging, NL). A trained and qualified person in compliance with national regulations will operate the digital chest X-ray.

  • POC-CRPDiagnostic test

    A quantitative POC-CRP LumiraDx (LumiraDx Limited, UK) triage test will be performed by finger-prick if CAD4TB scores is within the defined threshold window of study approach 2 triage testing

  • Xpert MTB/RIF UltraDiagnostic test

    Depending on CAD4TB (approach 1 \& 2) or POC-CRP score (approach 2) a confirmatory Xpert MTB/RIF Ultra(Cepheid, USA) rapid sputum molecular testing follows for both Mycobacterium tuberculosis complex and rifampicin resistance;

Study groups in NCT05526885
Study groupRoleWhat they receive
Approach 1 - CAD4TB screeningExperimentalParticipants with a CAD4TB version 7 (Delft Imaging, NL) score above the overall threshold (as defined for study approach 1) are eligible for Xpert MTB/RIF Ultra testing.
Receives: Diagnostic Test: CAD4TB; Diagnostic Test: Xpert MTB/RIF Ultra
Approach 2 - CAD4TB screening with POC-CRP triage testingExperimentalParticipants with a CAD4TB version 7 (Delft Imaging, NL) score within the threshold window (between lower and upper limit threshold as defined for study approach 2), a POC-CRP LumiraDx (LumiraDx Limited, UK) test will follow as a triage test. If CRP is above the determined threshold as defined for approach 2, Xpert MTB/RIF Ultra will be performed. If the CAD4TB score is above the upper limit threshold as defined for approach 2, Xpert MTB/RIF Ultra will be performed (without further CRP testing).
Receives: Diagnostic Test: CAD4TB; Diagnostic Test: POC-CRP; Diagnostic Test: Xpert MTB/RIF Ultra

What is being measured

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

  1. Yield of detected TB cases per study approach: number of positive Xpert MTB/RIF Ultra results per screening approach.

    Measured: 24 Months

  2. Cost-effectiveness of the CAD4TBv7-CRP approach using the CAD4TBv7 approach as a comparator: the costs for each positive Xpert Ultra case detected in the CAD4TBv7-CRP approach compared to the CAD4TBv7 approach

    Measured: 24 Months

Secondary outcomes (4)

  1. Extension of primary outcome: Cost-effectiveness of the CAD4TBv7-CRP approach and the CAD4TBv7 approach compared to passive case finding: cost per TB case detected

    Measured: 24 Months

  2. Equity analysis: 1. Socioeconomic status of households with actively detected TB cases compared to those with passively detected TB cases and to households with no TB cases: wealth quintiles distribution, income distribution and main source of income

    Measured: 24 Months

  3. Equity analysis: 2. Average out of pocket payments (OOP) associated with accessing TB treatment for households with identified TB cases across different wealth quintiles

    Measured: 24 months

  4. Health impact: The expected number of identified TB cases via passive case finding if the active case finding campaign had not taken place will be compared to the number of cases identified in the campaign

    Measured: 24 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 Sep 2022
  2. Study start7 Sep 2022
  3. Primary completion10 Dec 2024
  4. Study completion31 Dec 2024

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
Non-randomised
Intervention model
Single group
Model description
In this study a paired screen-positive design is used to directly compare two screening/triage approaches in the same individual based on a paired analysis: CAD4TB screening only (approach 1) versus CAD4TB screening with POC-CRP triage algorithm (approach 2).
Masking
None (open label)
Enrolment
20,000 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05526885
Sponsor's protocol ID
P1685-22B
Status last verified
Sep 2025
First submitted
31 Aug 2022
Last updated
22 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All data will be stored securely in a way that allows future access for the research team. We will adhere to the FAIR Guiding Principles for data management and stewardship. After completion of the studies and after anonymization (e.g. replace subject identifier with a new random subject identifier), analysis datasets will be made publicly available in a timely manner on a non-commercial data platform according to the FAIR principles.

Publications

  • Signorell A, van Heerden A, Ayakaka I, Jacobs BK, Antillon M, Tediosi F, Verjans A, Brugger C, Harkare HV, Labhardt ND, Bosman S, Kamele M, Keitseng M, Madonsela T, Kurscheid J, Muhairwe J, Keter AK, Murphy K, van Ginneken B, Gils T, Katende B, Gebresenbet RF, Erhardt RM, Zoller T, Vanobberghen F, Glass TR, Lynen L, Reither K. Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial. BMJ Open. 2025 Jul 28;15(7):e093989. doi: 10.1136/bmjopen-2024-093989.

    PubMed 40721262

  • Pita TP, Misra S, Madonsela T, Tshazi A, Bosman S, Ayakaka I, Vlieghe E, Decroo T, Reither K, van Heerden A, Gils T. "If your CD4 count lowers, that is when you are similar to a person that is non-existent" A qualitative exploration of perceptions around advanced HIV disease in South Africa. BMC Public Health. 2025 Jul 3;25(1):2325. doi: 10.1186/s12889-025-23588-1.

    PubMed 40610975

Questions about this trial

What is this clinical trial studying?

A study testing CAD4TB, POC-CRP and Xpert MTB/RIF Ultra in people with Tuberculosis, run by Klaus Reither 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 2 inclusion and 4 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 22 Sep 2025. 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 Lesotho, South Africa. 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?

Yield of detected TB cases per study approach: number of positive Xpert MTB/RIF Ultra results per screening approach. (time frame: 24 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 NCT05526885, 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 22 Sep 2025.

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