Diagnostic Accuracy of CAD4TB and C-reactive Protein Assay as Triage Tests for Pulmonary Tuberculosis (TB TRIAGE+)
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| ClinicalTrials.gov Identifier: NCT04666311 |
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Recruitment Status :
Completed
First Posted : December 14, 2020
Last Update Posted : September 9, 2022
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In the TB TRIAGE+ ACCURACY study, the accuracy of the following products will be determined:
- CAD4TB (Delft Imaging System, NL), a digital chest x-ray analysis software
- Afinion CRP assay (Alere Afinion, USA), which detects a cytokine induced acute phase protein
CAD4TB and the C-reactive protein assay are two tests with great potential of becoming a triage test for the diagnosis of tuberculosis (TB). These potential triage tests for TB are intended to serve as rule-out tests with a high sensitivity and negative predictive value.
Before impact and cost-effectiveness of new TB triage tests for intensified active case finding can be determined, the diagnostic test accuracy needs to be assessed in comparison to confirmatory reference tests. This accuracy study will define cut-off values for CAD4TB as well as for the Afinion CRP assay to be used in a future cluster-randomised trial on impact and cost-effectiveness of TB triage strategies for intensified active case finding in Lesotho and KwaZulu-Natal, South Africa.
A sub-study (detailed in a separate study protocol), hereafter called AHD-FEASIBILITY, explores the feasibility of implementing a series of point-of-care tests, including the new VISITECT CD4 Advanced Disease Test (Omega Diagnostics, UK) as part of the WHO-recommended advanced HIV Disease care package in the context of community-based HIV/TB campaigns.
Due to the coinciding pandemics and the overlapping symptoms of TB and COVID-19, it is critical to test for SARS-Cov-2 infections in the study population. In addition, this study will contribute to the evaluation of a novel SARS-Cov-2 antigen rapid diagnostic test (from the diagnostic pipeline of FIND) and CAD4COVID, a digital chest x-ray analysis software (Delft Imaging System, NL) in combination with differential white blood cell count.
| Condition or disease | Intervention/treatment |
|---|---|
| Pulmonary Tuberculosis Tuberculosis Diagnosis Covid-19 HIV | Diagnostic Test: Accuracy of CAD4TB and Afinion CRP assay for pulmonary TB Diagnostic Test: CAD4COVID+WBC and COVID-19 RDT for SARS-CoV-2 infection |
This is a prospective, partially blinded, two-centre cross-sectional study in which the diagnostic test accuracy of CAD4TB and an Afinion CRP assay test for TB will be assessed at facility level by evaluating a sample of 1400 adults (age ≥18years) with one or more TB symptoms (WHO recommended four-symptom screening; cough, weight loss, night sweats, fever) of any duration.
Presumptive TB patients will be recruited (i) at the outpatient departments of the Butha-Buthe District Hospital (Butha-Buthe, Lesotho) and the Caluza Clinic (Pietermaritzburg, KwaZulu-Natal, South Africa) and (ii) during community-based health campaigns by SolidarMed in Lesotho and HSRC in South Africa. Participants will be enrolled after giving written informed consent.
Study procedures comprise the following (detailed in the schedule of events): collection of contact, anthropometric, demographic and clinical data, HIV testing and counselling per national guidelines, collection of capillary blood for HIV testing, Afinion CRP assay, differential white blood cell count, VISITECT CD4 Advanced Disease Test (if HIV-positive), CrAg Lateral Flow Assay (if HIV positive and CD4 count <200 cells/μl as per VISITECT CD4 Advanced Disease Test, and no history of cryptococcal meningitis treatment); collection of urine (if HIV positive) for Alere Determine TB LAM Ag test; chest radiography for CAD4TB and CAD4COVID analysis and remote expert reading; nasopharyngeal swabs for SARS-Cov-2 real-time PCR and SARS-Cov-2 antigen test, collection of two spot sputa samples (S1,S2) for Xpert MTB/RIF, Xpert MTB/RIF Ultra (S1) and for mycobacterial culture [MGIT] (S2). At week 12 (±2weeks), we will contact each participant by phone and collect data on their vital status, and any TB treatment since enrolment. For individuals on TB treatment, further information, e.g. on reasons for empirical treatment, will be collected at the health facility the participant started TB treatment.
| Study Type : | Observational |
| Actual Enrollment : | 1400 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Prospective, Multicentre Evaluation of the Accuracy of CAD4TB and C-reactive Protein Assay as Triage Tests for the Diagnosis of Pulmonary Tuberculosis in Presumptive Adult TB Patients (TB TRIAGE+ Accuracy) |
| Actual Study Start Date : | February 15, 2021 |
| Actual Primary Completion Date : | April 5, 2022 |
| Actual Study Completion Date : | August 11, 2022 |
| Group/Cohort | Intervention/treatment |
|---|---|
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Adult presumptive TB cases
Adult presumptive TB cases (age ≥18years) with one or more TB symptoms (WHO recommended four-symptom screening; cough, weight loss, night sweats, fever) of any duration.
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Diagnostic Test: Accuracy of CAD4TB and Afinion CRP assay for pulmonary TB
CAD4TB version 6 and 7: Software tool for detecting lung abnormalities in computer tomogram images (pulmonary abnormalities) and frontal chest radiograph images (tuberculosis abnormalities) ; availability is guaranteed by Delft Imaging System; EC 0344 Certificate (vs.6); CE mark pending (vs.7). Will be performed by a registered and qualified radiographer in accordance with national regulations. Afinion AS100 Analyzer and Afinion CRP: In vitro diagnostic to determine the amount of CRP in human whole blood, serum or plasma; CE-mark ; Will be performed by qualified, GCP-trained study personnel. Diagnostic Test: CAD4COVID+WBC and COVID-19 RDT for SARS-CoV-2 infection CAD4COVID: Non-commercial product. Software tool for detecting pneumonia-related features to be expected in COVID-19 patients; availability is guaranteed by Delft Imaging System; CE certified. Will be performed by a registered and qualified radiographer/health professional in accordance with national regulations. Analysis in combination with differential white blood cell count. SD Biosensor, STANDARDTM Q COVID-19 Ag Test (rapid chromatographic immunoassay for the qualitative detection of specific antigens to SARS-CoV-2) |
- Determine CAD4TB cut-off value [ Time Frame: 15 months after first patient visit ]Receiver operating characteristic analysis (ROC) of CAD4TB against a composite microbiological reference standard (mycobacterial culture [MGIT] or Xpert MTB/RIF) to define an acceptable diagnostic cut-off value.
- Determine Afinion CRP assay cut-off value [ Time Frame: 15 months after first patient visit ]Receiver operating characteristic analysis (ROC) of Afinion CRP assay against a composite microbiological reference standard (mycobacterial culture [MGIT] or Xpert MTB/RIF) to define an acceptable diagnostic cut-off value.
- Evaluate CAD4TB ROC against reference standard [ Time Frame: 15 months after first patient visit ]Receiver operating characteristic analysis (ROC) of CAD4TB against a single microbiological reference standard (mycobacterial culture [MGIT] alone, Xpert MTB/RIF alone, Xpert MTB/RIF Ultra alone), against a composite reference standard and against a radiological reference standard
- Evaluate Afinion CRP assay ROC against reference standard [ Time Frame: 15 months after first patient visit ]Receiver operating characteristic analysis (ROC) of Afinion CRP assay against a single microbiological reference standard (mycobacterial culture [MGIT] alone, Xpert MTB/RIF alone, Xpert MTB/RIF Ultra alone) and against a composite reference standard
- Evaluate CAD4COVID and COVID-19 RDT ROC against reference standard [ Time Frame: 15 months after first patient visit ]Receiver operating characteristic analysis (ROC) of CAD4COVID combined with differential white blood cell count and point estimates of sensitivity and specificity the novel SARS-Cov-2 antigen rapid diagnostic test, both against a single microbiological reference standard (SARS-Cov-2 real-time PCR)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Adult presumptive TB cases (age ≥18years) with one or more TB symptoms (WHO recommended four-symptom screening; cough, weight loss, night sweats, fever) of any duration.
Presumptive TB patients will be recruited (i) at the outpatient departments of the Butha-Buthe District Hospital (Butha-Buthe, Lesotho) and the Caluza Clinic (Pietermaritzburg, KwaZulu-Natal, South Africa) and (ii) during community-based health campaigns by SolidarMed in Lesotho and HSRC in South Africa.
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)
- Any of the cardinal symptoms of TB (cough, weight loss, night sweats, fever) of any duration
Exclusion Criteria:
- Pregnancy (based on oral information from participant)
- Any condition for which participation in the study, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
- Critically sick patients who need immediate medical care
- Current anti-TB treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04666311
| Lesotho | |
| Butha-Buthe District Hospital | |
| Butha-Buthe, Lesotho | |
| South Africa | |
| Caluza Clinic | |
| Pietermaritzburg, KwaZulu-Natal, South Africa | |
| Principal Investigator: | Klaus Reither, MD, PhD | Swiss Tropical & Public Health Institute |
| Responsible Party: | Klaus Reither, Head of Clinical Research Unit, Swiss Tropical & Public Health Institute |
| ClinicalTrials.gov Identifier: | NCT04666311 |
| Other Study ID Numbers: |
P1685-20A |
| First Posted: | December 14, 2020 Key Record Dates |
| Last Update Posted: | September 9, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 20. 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. The principles of data sharing will be explained in the informed consent form. All data will be owned by the Sponsor-Investigator and investigators of TB TRIAGE+, while a Data Access Committee will review all requests for data sharing. |
| Time Frame: | 12 months after completion of the EDCTP-funded TB TRIAGE+ project |
| Access Criteria: | The Executive Group of the TB TRIAGE+ project will establish a Data Access Committee (DAC). The DAC will review all requests for data sharing. After approval by the DAC, the final verified and anonymised datasets and support for analysis will be made available to all relevant stakeholders, both at local level (health facility, region and country) as well as international decision makers (e.g. WHO) and interested research groups in order to advance research in TB. |
| 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 |
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Presumptive adult TB C Reactive Protein assay CAD4TB Point of Care Test TB Triage Test Diagnostic Accuracy |
CAD4COVID COVID-19 RDT Advanced HIV Disease (AHD) care package HIV testing Community-based triage testing for TB |
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COVID-19 Tuberculosis Tuberculosis, Pulmonary Disease Respiratory Tract Infections Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections |
Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases Pathologic Processes Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |