Performance Evaluation of the VIDAS TB-IGRA Assay.

This study will evaluate the performance of the VIDAS® Interferon Gamma (IFN-γ) Release Assay (TB-IGRA) assay, which is intended for use as an aid in the diagnosis of tuberculosis infection. This study is designed to assess (1) the sensitivity of this assay, (2) its percent agreement with other diagnostic tests, (3) its measurement precision , and (4) any potential interference of the presence of other non-tuberculosis mycobacterial bacterial infections with this assay.

Study Overview

• Status: Completed
• Conditions: Active Tuberculosis; Latent Tuberculosis Infection; Non-Tuberculous Mycobacterial (NTM) Pneumonia
• Intervention / Treatment: Diagnostic test: Blood draw and IGRA test

Detailed Description

Tuberculosis (TB) infection is one of the top 10 causes of death in the world and the leading cause of death due to a single infectious agent. Millions of people are infected with TB each year which can pose significant economic and health care burdens on the global population.

TB can infected the lungs (pulmonary TB) or other organs such as the brain, and kidneys (extra-pulmonary TB). When a person with pulmonary TB coughs or sneezes, water droplets containing M. tuberculosis are expelled into the air. Persons can become infected with TB when they inhale air containing these water droplets, however, not everyone infected with Mycobacterium tuberculosis (Mtb) becomes ill. Therefore two TB-related conditions exist: latent TB infection (LTBI) and TB disease.

People with latent TB infection are not ill and do not present TB symptoms or have TB disease. The only sign of TB infection is a positive reaction to the tuberculin skin test or TB blood tests such as IGRA tests. People with latent TB infection are not contagious and cannot spread TB infection to others.

Identification and treatment of LTBI can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two types of test are currently available for the identification of LTBI: the tuberculin skin test (TST) and the TB Interferon Gamma (IFN-γ) Release Assay (TB-IGRA). Evidence suggests that both TST and TB-IGRA are acceptable but not perfect because they detect indirect markers of Mtb exposure and indicate a cellular immune response to M. tuberculosis. TB-IGRAs have a number of advantages compared to TST which promote their progressive adoption in the clinical practice and in guidelines.

• Study Type: Observational
• Enrollment (Actual): 2401

Contacts and Locations

Study Locations

• Brazil
  • Campo Grande, Brazil
    • Universidade Federal de Mato Grosso do Sul (UFMS)
  • Dourados, Brazil
    • Universidade Federal Da Grande Dourados (UFGD)
• France
  • Chambéry, France
    • Anti-TB center of Chambéry
  • Montpellier, France
    • Lapeyronie Hospital
  • Nanterre Cedex, France
    • Anti-TB center of Nanterre
  • Paris, France
    • Lariboisiere Hospital
  • Paris, France
    • Avicenne Hospital
  • Saint-Étienne, France
    • North Hospital
• Georgia
  • Tbilisi, Georgia
    • National Center for Tuberculosis and Lung Disease
• India
  • Mumbai, India
    • Hinduja Hospital
• Italy
  • Rome, Italy
    • INMI L. Spallanzani
• Mexico
  • Mexicali, Mexico
    • Autonomous University of Baja California
• South Africa
  • Cape Town, South Africa
    • TASK Applied Science, Delft Day Hospital Premises
  • South Africa, South Africa
    • University of Cape Town Centre for Lung Infection and Immunity
• United Kingdom
  • London, United Kingdom
    • Royal Free Hospital
  • London, United Kingdom
    • Evelina London Children's Hospital
  • London, United Kingdom
    • St Thomas' Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92103
      • UC San Diego
  • Colorado
    • Denver, Colorado, United States, 80206
      • Naional Jewish Health
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois- Chicago
  • Missouri
    • Saint Louis, Missouri, United States, 63103
      • Saint Louis University
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll persons with low to high risk factors for acquiring TB infection, persons with active TB disease, and persons with other types of Mycobacterial infections

Description

Active TB Population

Inclusion Criteria:

A person classified as or suspected of having M. tuberculosis disease (active TB):

A person with known HIV status, determined by a laboratory or rapid test performed no earlier than one month prior to, or at the time of inclusion into this study A person of age ≥ 2 years

Exclusion Criteria:

A person who has been on an anti-TB treatment for >15 days for the ongoing infection Pregnant women A person who has received an anti-tumor necrosis factor (TNF) alpha treatment within the previous 3 months A person who has had prior TST A person with an NTM infection A person with positive HIV status.

High Risk for TB infection

Inclusion criteria :

A person who is at increased risk for M. tuberculosis infection (and therefore LTBI) and/or for progression to active TB:

A person with age ≥ 2 years A person with known HIV status

Non-inclusion criteria will be:

A person who has or has had active TB A person who has received treatment for active TB or LTBI A person who has received an anti-TNF alpha treatment A person who has had a TST Pregnant women Person who has been an NTM infection

Low Risk for TB Infection

Inclusion criteria

Generally healthy people, unlikely to have encountered TB disease in the past, that may be subject to TB testing for professional, academic or personal reasons (e.g.: students, healthcare personnel and healthcare volunteers, military recruits) A person with age ≥ 18 years old

Non-inclusion criteria A person who is considered at high risk for LTBI A person who has or has had active TB A person who has received treatment for active TB or LTBI A person who has received an anti-TNFalpha treatment A person who has had a TST Pregnant women A person who has been diagnosed with a NTM infection

NTM population:

Inclusion criteria A person who is positive for NTM of interest confirmed by culture and identification;

Non-inclusion criteria A person who has been on antibiotic treatment for NTM; A person with confirmed active TB; A person with HIV; A person with a history of active TB; A person who have received treatment for LTBI; A person who is at high risk for LTBI Pregnant women.

Precision Population

Inclusion criteria:

A person previously enrolled in the Active TB, High Risk or Low Risk studies, or a blood donor.

Non-inclusion criteria An adult who was not previously enrolled in the Active TB, High Risk or Low Risk studies except for blood donors

For blood donors only:

A person who can be classified as being at increased risk for M. tuberculosis infection (and therefore LTBI) and/or for progression to active TB

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Active Tuberculosis Patient	Diagnostic test: Blood draw and IGRA test; One to two blood samples will be obtained from participants in all arms in order to conduct testing.
High risk for LTBI Participant	Diagnostic test: Blood draw and IGRA test; One to two blood samples will be obtained from participants in all arms in order to conduct testing.
Low risk for prior TB infection Participant	Diagnostic test: Blood draw and IGRA test; One to two blood samples will be obtained from participants in all arms in order to conduct testing.
NTM patient	Diagnostic test: Blood draw and IGRA test; One to two blood samples will be obtained from participants in all arms in order to conduct testing.
Precision patient	Diagnostic test: Blood draw and IGRA test; One to two blood samples will be obtained from participants in all arms in order to conduct testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive, negative, indeterminate for tuberculosis	The VIDAS or comparator assays will qualitatively determine the presence or absence of Mycobacterial TB infection in a participant's blood. This measurement is based on the level of interferon gamma released after stimulation of T cells in blood.	One-time measurement through study completion for each participant, an average of 5 months.
Sensitivity and positive and negative percent agreement for the VIDAS TB IGRA assay with comparator assay	Results obtained using the VIDAS assay will be compared with the results obtained from other methods.	One-time measurement through study completion for each participant, an average of 5 months.
Degree of Interference by nontuberculous mycobacteria for the VIDAS TB IGRA assay	Persons with NTM will be tested using the VIDAS TB IGRA.	One-time measurement through study completion for each participant, an average of 5 months.
Measurement Precision of the VIDAS TB IGRA assay results	6- 4mL blood samples will be collected from each participant and tested using different VIDAS instruments.	Triplicate measurement per sample through study completion, an average of 5 months.

Collaborators and Investigators

• Sponsor: BioMérieux
• Investigators: Principal Investigator: David Pride, UC San Diego; Principal Investigator: Maria Gennaro, Rutgers University; Principal Investigator: Michael Lauzardo, University of Florida; Principal Investigator: Niaz Banaei, Stanford University; Principal Investigator: Nahed Ismail, University of Illinois Chicago; Principal Investigator: Daniel Hoft, St. Louis University; Principal Investigator: Charles Daley, National Jewish Health; Principal Investigator: Amanda Lopes, Lariboisiere Hospital; Principal Investigator: Frederic Méchaï, Avicenne Hospital; Principal Investigator: Florence Doucet-Populaire, Antoine-Béclère Hospital; Principal Investigator: Elisabeth Botelho-Nevers, North Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 14, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Tuberculosis; Interferon Gamma Release Assay
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Tuberculosis; Latent Tuberculosis
• Other Study ID Numbers: B2694-CTPR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No