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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

Primary Purpose

Tuberculosis

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
CAD4TB
POC-CRP
Xpert MTB/RIF Ultra
Sponsored by
Klaus Reither
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Tuberculosis focused on measuring Lesotho, South Africa, community-based, tuberculosis, active case findings, cost-effectiveness, CAD4TB, POC-CRP, Xpert MTB/RIF Ultra, triage, screening

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts 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
  • Lesotho only: Pregnancy (self-reported)

Sites / Locations

  • SolidarMedRecruiting
  • Human Sciences Research CouncilRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Approach 1 - CAD4TB screening

Approach 2 - CAD4TB screening with POC-CRP triage testing

Arm 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.

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)
Economic costs of approach 1 versus approach 2 of the TB active-case finding campaign

Full Information

First Posted
August 31, 2022
Last Updated
December 2, 2022
Sponsor
Klaus Reither
Collaborators
SolidarMed Lesotho, Institute of Tropical Medicine, Belgium, Radboud University Medical Center, Charite University, Berlin, Germany, Human Sciences Research Council
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1. Study Identification

Unique Protocol Identification Number
NCT05526885
Brief 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
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2022 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Klaus Reither
Collaborators
SolidarMed Lesotho, Institute of Tropical Medicine, Belgium, Radboud University Medical Center, Charite University, Berlin, Germany, Human Sciences Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Lesotho, South Africa, community-based, tuberculosis, active case findings, cost-effectiveness, CAD4TB, POC-CRP, Xpert MTB/RIF Ultra, triage, screening

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
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)
Allocation
Non-Randomized
Enrollment
20000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Approach 1 - CAD4TB screening
Arm Type
Experimental
Arm 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.
Arm Title
Approach 2 - CAD4TB screening with POC-CRP triage testing
Arm Type
Experimental
Arm 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).
Intervention Type
Diagnostic Test
Intervention Name(s)
CAD4TB
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
POC-CRP
Intervention Description
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
Intervention Type
Diagnostic Test
Intervention Name(s)
Xpert MTB/RIF Ultra
Intervention Description
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;
Primary Outcome Measure Information:
Title
Yield of detected TB cases per study approach: number of positive Xpert MTB/RIF Ultra results per hypothetical study approach.
Time Frame
24 Months
Title
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.
Time Frame
24 Months
Secondary Outcome Measure Information:
Title
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)
Time Frame
24 Months
Title
Economic costs of approach 1 versus approach 2 of the TB active-case finding campaign
Time Frame
24 Months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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 Lesotho only: Pregnancy (self-reported)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Klaus Reither, MD, PhD
Phone
+41612848967
Email
klaus.reither@swisstph.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Aita Signorell, PhD
Phone
+41612848969
Email
aita.signorell@swisstph.ch
Facility Information:
Facility Name
SolidarMed
City
Maseru
Country
Lesotho
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irene Ayakaka, Dr.
Facility Name
Human Sciences Research Council
City
Pietermaritzburg
State/Province
KwaZulu-Natal
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alastair van Heerden, Prof.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
Links:
URL
https://tbtriage.com/
Description
Project website

Learn more about this trial

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

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