Evaluating the Accuracy of New Tests for TB Infection Diagnosis

NCT06221735 | Completed DMC

• 1 other identifier: TBI Testing
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: The large reservoir of tuberculosis infections is a key driver of sustained tuberculosis (TB) incidence. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The Cy-TB skin test and STANDARD F TB-Feron FIA (TB-Feron) fluorescent immunoassay are two newly developed TB infection tests, which could offer quality and cost advantages over other commercially available TB infection tests, especially the standard TST test. Both tests have a higher sensitivity and specificity than the currently most used tuberculin skin test. The proposed study aims to evaluate the performance of these two tests for the diagnosis of TB infection, compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay. Methods and analysis: This diagnostic accuracy study will employ a cross-sectional, observational design that aims to assess the accuracy of the Cy-TB and TB-Feron tests for diagnosing TB infection, using the QFT-Plus assay as the reference standard. The sensitivity and specificity will be reported. Three different cohorts of study participants will be recruited: Adults with microbiologically-confirmed pulmonary TB (n=100); Household contacts\* of people with TB (n=200) and negative controls\*\* (n=50). All participants will be examined with Cy-TB, TB-Feron, and QFT-Plus. \*Household contacts: of a person with TB are defined as members who live under the same roof as the person with pulmonary tuberculosis (PTB) or who meet the following conditions:

• Sleeping under the same roof or sharing a kitchen space as PTB-affected persons at least one night/week for three months before the person was diagnosed with PTB
• Staying under the same roof with PTB-affected persons for at least one hour/day and continuously five days/week for three months before the person was diagnosed with PTB
• Negative controls are defined as people with a negative QFT-Plus result in the past year and likely to have no or very low rates of TB exposure history.

Conditions

Latent Tuberculosis; TB Infection; Tuberculosis

Keywords

Tuberculosis; TB Infection; LTBI; TBI

Outcome Measures

Primary Outcomes (1)

• Sensitivity

  Point estimates of sensitivity with 95% confidence interval for the Cy-TB and TB-Feron tests, using the QFT-Plus assay as the reference standard

  From study entry at the time of blood collection and Cy-TB injection until 72 hours post-injection, reported at the end of the trial.

Secondary Outcomes (1)

• Specificity

  From study entry at the time of blood collection and Cy-TB injection until 72 hours post-injection, reported at the end of the trial.

Study Arms (3)

Cy-TB test

EXPERIMENTAL

The study will include people with confirmed TB infection and negative controls to compare the specificity and sensitivity of the Cy-TB and TB-Feron tests versus the QFT-Plus assay

Diagnostic Test: Cy-TB test; Diagnostic Test: STANDARD F TB-Feron FIA test

STANDARD F TB-Feron FIA test

EXPERIMENTAL

The study will include people with confirmed TB infection and negative controls to compare the specificity and sensitivity of the Cy-TB and TB-Feron tests versus the QFT-Plus assay

Diagnostic Test: Cy-TB test; Diagnostic Test: STANDARD F TB-Feron FIA test

QuantiFERON-TB Gold Plus assay

ACTIVE COMPARATOR

The QuantiFERON-TB Gold Plus assay will be used as the study's reference standard

Diagnostic Test: Cy-TB test; Diagnostic Test: STANDARD F TB-Feron FIA test

Interventions

Cy-TB test DIAGNOSTIC_TEST

The study will include people with confirmed TB infection and negative controls to compare the specificity and sensitivity of the Cy-TB and TB-Feron tests versus the QFT-Plus assay

Also known as: C-TB

Cy-TB test; QuantiFERON-TB Gold Plus assay; STANDARD F TB-Feron FIA test

STANDARD F TB-Feron FIA test DIAGNOSTIC_TEST

The study will include people with confirmed TB infection and negative controls to compare the specificity and sensitivity of the Cy-TB and TB-Feron tests versus the QFT-Plus assay

Also known as: TB-Feron

Cy-TB test; QuantiFERON-TB Gold Plus assay; STANDARD F TB-Feron FIA test

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants:
• Agree to remain in contact and provide updated information as necessary, and have no current plans to relocate outside the designated area for the duration of the study
• Capable of providing signed informed consent and informed assent (as appropriate)
• Group 1:
• \+ Microbiologically-confirmed pulmonary TB (either drug-susceptible TB or drug-resistant TB) via Xpert MTB/RIF or Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, California) and abnormal chest X-ray (CXR) result\*
• \*To reduce the false positive rate of molecular diagnostic assays for M. tuberculosis
• Group 2:
• \+ Household contacts without symptoms of active TB disease of people with microbiologically-confirmed, pulmonary TB who initiated treatment with residents in Ha Noi, Vietnam.
• Group 3:
• Known past negative IGRA test results among those at low risk for TB infection
• No known and/or reported history of contact or exposure to either TB disease or M. tuberculosis bacteria.

You may not qualify if:

• All participants:
• \+ Declines to provide informed consent to participate in the study
• Groups 2 \&3:
• Presumed TB disease with symptoms (cough, fever, night sweats, unintentional weight loss) and/or an abnormal CXR result suggestive of TB disease
• Microbiologically - or clinically-confirmed TB disease in all forms or report having taken treatment for TB disease.
• History of TB infection (self-record or documented).

Sponsors & Collaborators

• Freundeskreis Für Internationale Tuberkulosehilfe e.V: lead

Study Sites (1)

Vietnam National Lung Hospital

Hà Nội, 10000, Vietnam

Location

Related Publications (1)

• Nguyen HT, Vo LNQ, Codlin A, Forse R, Wingfield T, Sidney K, MacLean EL, Creswell J, Kirubi B, Davies Forsman L. Study protocol: diagnostic accuracy study comparing Cy-Tb and STANDARD F TB-Feron FIA tests for tuberculosis infection diagnosis in Vietnam. BMJ Open. 2024 Aug 9;14(8):e085614. doi: 10.1136/bmjopen-2024-085614.

  PMID: 39122402 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be injected with Cy-TB and the results will be read after 48-72 hours. 10 mL of blood will be obtained from each participant and transferred to three TB-Feron tubes and four QFT-Plus tubes whereby the tubes will be incubated at 37℃ for 16 to 24 hours. The TB-Feron tubes will be analyzed with the fully automated STANDARD F2400 device, while QFT-Plus tubes will be analyzed using an ELISE microplate reader

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: January 24, 2024
• Study Start: June 11, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 19, 2025

Record last verified: 2025-03

Locations

VN (1)