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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05526885
• Other study ID #: P1685-22B
• Status: Recruiting
• Phase: N/A
• Start date: September 7, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Swiss Tropical & Public Health Institute
• Contact: Klaus Reither, MD, PhD
• Phone: +41612848967
• Email: klaus.reither[@]swisstph.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: December 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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
• Lesotho only: Pregnancy (self-reported)

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Diagnostic Test:
• CAD4TB
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-CRP
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 Ultra
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;

Locations

Country	Name	City	State
Lesotho	SolidarMed	Maseru
South Africa	Human Sciences Research Council	Pietermaritzburg	KwaZulu-Natal

Sponsors (6)

Lead Sponsor	Collaborator
Klaus Reither	Charite University, Berlin, Germany, Human Sciences Research Council, Institute of Tropical Medicine, Belgium, Radboud University Medical Center, SolidarMed Lesotho

Countries where clinical trial is conducted

Lesotho,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Yield of detected TB cases per study approach: number of positive Xpert MTB/RIF Ultra results per hypothetical study approach.		24 Months
Primary	Cost-effectiveness of approach 2 using approach 1 as a comparator: the incremental (differential) costs per for each additional positive Xpert MTB/RIF Ultra case detected in approach 2 compared to approach 1.		24 Months
Secondary	Yield of detected TB cases per study approach in defined subgroups (HIV infected vs. uninfected participants, participants with and without TB history and with and without TB symptoms)		24 Months
Secondary	Economic costs of approach 1 versus approach 2 of the TB active-case finding campaign		24 Months

External Links

•   Project website