Clinical trial NCT05526885: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
Keywords: Lesotho
South Africa
community-based
tuberculosis
active case findings
cost-effectiveness
CAD4TB
POC-CRP
Xpert MTB/RIF Ultra
triage
screening
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: SolidarMed
name: Institute of Tropical Medicine, Belgium
name: Radboud University Medical Center
name: Charite University, Berlin, Germany
name: Human Sciences Research Council
First posted: 2022-09-02
Enrollment: 20000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention 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).
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Yield of detected TB cases per study approach: number of positive Xpert MTB/RIF Ultra results per screening approach.
timeFrame: 24 Months
measure: 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
timeFrame: 24 Months
Secondary outcomes:
measure: 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
timeFrame: 24 Months
measure: 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
timeFrame: 24 Months
measure: Equity analysis: 2. Average out of pocket payments (OOP) associated with accessing TB treatment for households with identified TB cases across different wealth quintiles
timeFrame: 24 months
measure: 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
timeFrame: 24 months
Other outcomes:
Locations:
city: Maseru
country: Lesotho
facility: SolidarMed
city: Pietermaritzburg
country: South Africa
facility: Human Sciences Research Council
state: KwaZulu-Natal
Study officials:
References: