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

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.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis, Extrapulmonary
• Intervention / Treatment: Diagnostic test: IRISA-TB

• Study Type: Interventional
• Enrollment (Estimated): 2160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louié E Kühn, MBChB; Phone Number: +27216505981; Email: louie.kuhn@uct.ac.za
• Study Contact Backup: Name: Aliasgar Esmail, MD FCP; Phone Number: +27214066119; Email: ali.esmail@uct.ac.za

Study Locations

• South Africa
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa
      • Not yet recruiting
      • University of KwaZulu-Natal
      • Contact: Kennedy Nyamande; Email: nyamandek@ukzn.ac.za
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • Recruiting
      • University of Cape Town Lung Institute
      • Contact: Keertan Dheda, MD/PhD; Email: keertan.dheda@uct.ac.za
      • Contact: Ali Esmail, MD; Email: a.esmail@uct.ac.za
      • Principal Investigator: Louié E Kühn, MBChB
• Zambia
  • Lusaka, Zambia
    • Not yet recruiting
    • ZAMBART
    • Contact: Omar Siddiqi, MD; Email: osiddiqi@bidmc.harvard.edu
    • Principal Investigator: Kondwelani Mateyo, MD
• Zimbabwe
  • Harare, Zimbabwe
    • Not yet recruiting
    • Biomedical Research and Training Institute
    • Contact: Junior Mutsvangwa, MBChB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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)
2. Patients with current significant history of substance or alcohol abuse that may impact study visits.
3. Patients who are unable to communicate by telephone or who do not have a current active traceable contact number.
4. Patients not willing to undergo an HIV test.
5. Patients whose fluid sample volumes are insufficient to perform standard of care testing in addition to IRISA-TB
6. Positive sputum GXP within 2 weeks prior to serosal fluid or CSF sampling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test-specific performance outcomes	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)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Empiric treatment rates for extrapulmonary TB	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.	24 months
Cost effectiveness	Determining the true cost to the health system of various diagnostic strategies.	24 months.

Collaborators and Investigators

• Sponsor: University of Cape Town
• Collaborators: University of Cape Town Lung Institute; Leiden University Medical Center; European Union; Biomedical Research and Training Institute; Zambart
• Investigators: Principal Investigator: Aliasgar Esmail, MD FCP, UCT Lung Institute, Centre for lung infection and immunity

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Estimated): November 16, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Tuberculosis; Interferon-gamma; Tuberculosis diagnostics
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Infections; Inflammation; Central Nervous System Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Tuberculosis, Central Nervous System; Neuroinflammatory Diseases; Tuberculosis; Meningitis; Tuberculosis, Meningeal; Tuberculosis, Extrapulmonary; Serositis
• Other Study ID Numbers: Epi-TB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No