Epi-TB: Same Day Diagnosis of Extrapulmonary TB (TB Serositis and TB Meningitis).

Sponsor

University of Cape Town (Other)

Overall Status

Recruiting

CT.gov ID

NCT06135818

Collaborator

European Union (Other), Zambart (Other), Biomedical Research and Training Institute (Other), Leiden University Medical Center (Other), University of Cape Town Lung Institute (Other)

2,160

Enrollment

Locations

Arm

62.5

Anticipated Duration (Months)

540

Patients Per Site

8.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Extrapulmonary TB (EPTB) accounts for nearly 30% of TB cases in HIV endemic settings, such as South Africa. The diagnosis of extrapulmonary TB is complicated by the poor performance of Gene Xpert and TB Culture in extrapulmonary fluid (30-50% sensitive), as well as the poor specificity of ADA. We can therefore not reliably use these tests to diagnose EPTB as effectively as we use them in sputum samples. The current best practice for diagnosing pleural TB is to perform a pleural biopsy, which is both invasive and costly. A rapid, easy to use test is needed to allow accurate and fast diagnosis of EPTB. Interferon-gamma is released at high concentrations in extrapulmonary fluid in active EPTB. Antrum Biotech has developed the IRISA-TB assay (validated and SAHPRA licenced) for the diagnosis of EPTB.

The study will assess the real-world performance of IRISA-TB compared to ADA, Gene Xpert, and TB Culture when used to diagnose EPTB. We will evaluate IRISA-TB's performance in the following patient groups:

Suspected TB pleural effusion (n= 650)
Suspected TB pericardial effusion (n= 280)
Suspected TB peritonitis (n= 200)
Suspected TB meningitis (n = 1040) As part of our evaluation, we will ask clinicians who treat these patients to provide their feedback on IRISA-TB. We will ask them to indicate to what extent the IRISA-TB test helped them to make treatment decisions. Finally, we will conduct an economic assessment to determine the true cost of diagnosing and treating EPTB to the health system and patients, and we will determine how IRISA-TB could potentially result in cost savings.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis, Extrapulmonary	Diagnostic Test: IRISA-TB	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2160 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Prospective cohortProspective cohort

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Same Day Diagnosis of Extrapulmonary TB (TB Serositis and TB Meningitis).

Actual Study Start Date :

Mar 16, 2021

Anticipated Primary Completion Date :

May 31, 2025

Anticipated Study Completion Date :

May 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with suspected extrapulmonary tuberculosis Patients with pleural, pericardial, or peritoneal effusions due to suspected extrapulmonary tuberculosis and those with suspected TB meningitis.	Diagnostic Test: IRISA-TB ELISA-based assay that detects interferon-gamma concentrations in extrapulmonary fluid in active TB.

Arm

Intervention/Treatment

Experimental: Patients with suspected extrapulmonary tuberculosis

Patients with pleural, pericardial, or peritoneal effusions due to suspected extrapulmonary tuberculosis and those with suspected TB meningitis.

Diagnostic Test: IRISA-TB

ELISA-based assay that detects interferon-gamma concentrations in extrapulmonary fluid in active TB.

Outcome Measures

Primary Outcome Measures

Test-specific performance outcomes [24 months]
Comparison of sensitivity, specificity, accuracy, predictive values, likelihood ratios, number needed to treat (NNT) and indeterminate rate for the various diagnostic assays (IRISA-TB, ADA, Gene Xpert, TB Culture)

Secondary Outcome Measures

Empiric treatment rates for extrapulmonary TB [24 months]
Clinicians will be asked to indicate whether IRISA-TB made an impact on treatment decisions. Empiric treatment rates for extrapulmonary TB are high due to poor performance of current diagnostics.
Cost effectiveness [24 months.]
Determining the true cost to the health system of various diagnostic strategies.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female participants 18 years and over attending health care facility with symptoms of TB.
Serosal or CSF fluid sample provided to NHLS with sufficient volume to perform SOC tests + 1ml.
Patients in whom extrapulmonary TB is part of the treating clinicians' differential diagnosis.

Exclusion Criteria:

Volunteers who refuse to sign informed consent and/or provide clinical details (Proxy consent will be obtained for participants who are incapacitated, with a follow up consent when they have recovered their capacity to consent)
Patients with current significant history of substance or alcohol abuse that may impact study visits.
Patients who are unable to communicate by telephone or who do not have a current active traceable contact number.
Patients not willing to undergo an HIV test.
Patients whose fluid sample volumes are insufficient to perform standard of care testing in addition to IRISA-TB
Positive sputum GXP within 2 weeks prior to serosal fluid or CSF sampling.

Contacts and Locations

Locations

	Site	City	State	Country
1	University of KwaZulu-Natal	Durban	KwaZulu-Natal	South Africa
2	University of Cape Town Lung Institute	Cape Town	Western Cape	South Africa
3	Zambart	Lusaka		Zambia
4	Biomedical Research and Training Institute	Harare		Zimbabwe