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
1 other identifier
interventional
20,000
2 countries
2
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Sep 2022
Typical duration for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2022
CompletedFirst Posted
Study publicly available on registry
September 2, 2022
CompletedStudy Start
First participant enrolled
September 7, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 10, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedSeptember 22, 2025
September 1, 2025
2.3 years
August 31, 2022
September 16, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Yield of detected TB cases per study approach: number of positive Xpert MTB/RIF Ultra results per screening approach.
24 Months
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
24 Months
Secondary Outcomes (4)
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
24 Months
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
24 Months
Equity analysis: 2. Average out of pocket payments (OOP) associated with accessing TB treatment for households with identified TB cases across different wealth quintiles
24 months
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
24 months
Study Arms (2)
Approach 1 - CAD4TB screening
EXPERIMENTALParticipants 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.
Approach 2 - CAD4TB screening with POC-CRP triage testing
EXPERIMENTALParticipants 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).
Interventions
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.
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
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;
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Klaus Reitherlead
- SolidarMedcollaborator
- Institute of Tropical Medicine, Belgiumcollaborator
- Radboud University Medical Centercollaborator
- Charite University, Berlin, Germanycollaborator
- Human Sciences Research Councilcollaborator
Study Sites (2)
SolidarMed
Maseru, Lesotho
Human Sciences Research Council
Pietermaritzburg, KwaZulu-Natal, South Africa
Related Publications (2)
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.
PMID: 40721262RESULTPita 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.
PMID: 40610975DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Head of Clinical Research Unit
Study Record Dates
First Submitted
August 31, 2022
First Posted
September 2, 2022
Study Start
September 7, 2022
Primary Completion
December 10, 2024
Study Completion
December 31, 2024
Last Updated
September 22, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
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.