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

Klaus Reither

Status: Completed

Conditions: Tuberculosis

Treatments: Diagnostic Test: Xpert MTB/RIF Ultra; Diagnostic Test: POC-CRP; Diagnostic Test: CAD4TB

Study type: Interventional

Funder types: Other

Identifiers

NCT05526885

P1685-22B

Details and patient eligibility

About

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.

Enrollment: 20,000 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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 design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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20,000 participants in 2 patient groups

Approach 1 - CAD4TB screening

Experimental group

Description:

Participants 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.

Treatment:

Diagnostic Test: CAD4TB

Diagnostic Test: Xpert MTB/RIF Ultra

Approach 2 - CAD4TB screening with POC-CRP triage testing

Experimental group

Description:

Participants 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).

Treatment:

Diagnostic Test: CAD4TB

Diagnostic Test: POC-CRP

Diagnostic Test: Xpert MTB/RIF Ultra