T Cell Interferon-Gamma Release Assay (TIGRA) in Immunocompromised Individuals

Condition(s) targeted: Tuberculosis; Monitoring, Immunologic

Phase: N/A

Status: Recruiting

Sponsored by: Tuberculosis Network European Trialsgroup

Official(s) and/or principal investigator(s):
Martina Sester, PhD, Principal Investigator, Affiliation: Department of Internal Medicine IV, University of the Saarland, 66421 Homburg
Christoph Lange, MD, PhD, Study Chair, Affiliation: Div. of Clinical Infectious Diseases, Medical Clinic, Research Center Borstel, Germany

Overall contact:
Martina Sester, PhD, Phone: 49-684-116, Ext: 23557, Email: martina.sester@uks.eu

Until recently, the tuberculin skin test (TST) was the only available diagnostic assay for detection of latent infection with M. tuberculosis (LTBI). Despite the low overall incidence of symptomatic tuberculosis infection in low-prevalence countries, the potential mortality and morbidity mandate constant vigilance to identify patients at risk for reactivation. Due to systemic immunosuppression, immunocompromised patients with latent M. tuberculosis infection are at increased risk of progression to active disease. This applies to patients with various causes of immunodeficiency such as HIV-infected patients, allogeneic stem cell and solid organ transplant recipients, patients with rheumatoid arthritis and patients with chronic renal failure. Therefore, current guidelines aimed at preventing tuberculosis infection in immunocompromized individuals recommend a generalized screening for evidence of latent infection to target appropriate preventative prophylaxis. At present, tuberculosis control programs exclusively rely on the tuberculin skin test to identify a latent infection in asymptomatic individuals.

Recently, novel in vitro assays termed T cell interferon-gamma release assay (TIGRA) have become available that are based on the detection of interferon-gamma (IFN-gamma) production in T cells or supernatants after stimulation with highly specific antigens of M. tuberculosis. Two TIGRA are commercially available, the ELISPOT based T. SPOT. TB and the ELISA based QuantiFERON-TB Gold test (now available as an "IN-TUBE" version).

The aim of the study is a prospective comparison of the two commercially available approved TIGRA (QuantiFERON-TB Gold In-Tube and T. SPOT. TB) with the established Mendel-Mantoux skin-test in immunocompromized patients (main focus on sensitivity and specificity).

The study hypotheses are as follows:

1. In immunocompromised patients, the two commercially available approved TIGRA (QuantiFERON-TB Gold In-Tube and T. SPOT. TB) have increased sensitivity and specificity as compared to the established Mendel-Mantoux skin-test.

2. Results from QuantiFERON-TB Gold In-Tube and T. SPOT. TB do not differ in immunocompromised patients.

Official title: Prospective Head-to-Head Comparison of the Two Commercially Available Approved TIGRA (QuantiFERON-TB Gold In-Tube and T.SPOT.TB) With the Established Mendel-Mantoux Skin-Test in Immunocompromized Patients

Study design: Cohort, Prospective

Detailed description: Until recently, the tuberculin skin test (TST) was the only available diagnostic assay for detection of latent infection with M. tuberculosis (LTBI). Despite the low overall incidence of symptomatic tuberculosis infection in low-prevalence countries, the potential mortality and morbidity mandate constant vigilance to identify patients at risk for reactivation. Due to systemic immunosuppression, immunocompromised patients with latent M. tuberculosis infection are at increased risk of progression to active disease. This applies to patients with various causes of immunodeficiency such as HIV-infected patients, allogeneic stem cell and solid organ transplant recipients, patients with rheumatoid arthritis and patients with chronic renal failure. Therefore, current guidelines aimed at preventing tuberculosis infection in immunocompromized individuals recommend a generalized screening for evidence of latent infection to target appropriate preventative prophylaxis. At present, tuberculosis control programs exclusively rely on the tuberculin skin test to identify a latent infection in asymptomatic individuals.

Recently, novel in vitro assays termed T cell interferon-gamma release assay (TIGRA) have become available that are based on the detection of interferon-gamma (IFN-gamma) production in T cells or supernatants after stimulation with highly specific antigens of M. tuberculosis. Two TIGRA are commercially available, the ELISPOT based T. SPOT. TB and the ELISA based QuantiFERON-TB Gold test (now available as an "IN-TUBE" version). Current evidence suggests that TIGRA based on cocktails containing ESAT-6 and CFP-10 have the potential to become useful diagnostic tools. It has, however, been shown, that rates of indeterminate and positive results may differ between both tests, suggesting that they might provide different results in routine clinical practice. Moreover, there is only inadequate evidence on the value of those TIGRA in the management of immunocompromised individuals. Based on the current literature and most recent meta-analyses, there is an urgent need for head-to-head comparative studies of the two commercially available tests in immunocompromised patients. This study is designed to carry out a head-to-head comparison of the T. SPOT. TB and the ELISA based QuantiFERON-TB Gold In-Tube test with the TST in immunosuppressed populations. In a second step that will be addressed at a later stage, this study may be extended to longitudinally assess the predictive value of a positive blood test for progression to active disease.

The study will be performed within the tuberculosis network european trialsgroup (TBNET). It will be performed in a multicenter setting involving 23 participating centers from a total of 14 european countries. The study aims to include a total of 1800 study subjects distributed as follows: 200 HIV infected individuals with high and low CD4 T cells/µl (above and below 250 CD4 T cell/µl), respectively, 200 patients with chronic renal failure, 200 stem cell transplant recipients, 200 solid organ transplantation (lung, liver, kidney, kidney-pancreas) patients, 200 patients with rheumatoid arthritis. In addition, 200 immunocompromised patients with confirmed tuberculosis, 200 immunocompetent individuals with similar risk factors as patients, and 200 immunocompetent controls with no known risk of exposure or tuberculosis will serve as control groups.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Individual as specified for the study population

- Written informed consent

- Indication to perform tuberculin skin test(suspect latent infection, according to

standard guidelines, differential diagnosis)

Exclusion Criteria:

- <18 years of age

Martina Sester, PhD, Phone: 49-684-116, Ext: 23557, Email: martina.sester@uks.eu

Cellestis Limited, Carnegie, Australia; Active, not recruiting

National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria; Recruiting
Roumiana Markova, MD, PhD, Email: roumiana_markova@yahoo.com
Roumiana Markova, MD, PhD, Principal Investigator

Herlev Hospital, Herlev, Denmark; Active, not recruiting

Rheumatology and Center for Drug Research, Development and Safety, Frankfurt, Germany; Recruiting
Frank Behrens, MD, Email: Frank.Behrens@kgu.de
Frank Behrens, MD, Principal Investigator

Research Center Borstel, Borstel, Germany; Recruiting
Christoph Lange, MD, PhD, Email: clange@fz.borstel.de
Christoph Lange, MD, PhD, Principal Investigator
Martin Ernst, PhD, Sub-Investigator

University of the Saarland, Homburg, Germany; Recruiting
Martina Sester, PhD, Email: martina.sester@uks.eu
Martina Sester, PhD, Principal Investigator

Department of Infectious Diseases, Univ. of Freiburg, Freiburg, Germany; Recruiting
Dirk Wagner, MD, Email: wagnerdirk@Medizin.Ukl.Uni-Freiburg.De
Dirk Wagner, MD, Principal Investigator

HIV Treatment and Clinical Research Unit, Frankfurt, Germany; Recruiting
Timo Wolf, MD, Email: Timo.Wolf@kgu.de
Timo Wolf, MD, Principal Investigator

Respiratory Medicine, University of Thessaly, Mezourlo-Larissa, Greece; Recruiting
Irini Gerogianni, PhD, Email: igerogianni@yahoo.gr
Irini Gerogianni, PhD, Principal Investigator

Emerging Bacterial Pathogens Unit, Milan, Italy; Recruiting
Daniela M Cirillo, MD, PhD, Email: cirillo.daniela@hsr.it
Daniela M Cirillo, MD, PhD, Principal Investigator
Alberto Matteelli, MD, Sub-Investigator

National Institute for Infectious Diseases L. Spallanzani, Roma, Italy; Recruiting
Delia Goletti, MD, PhD, Email: d.goletti@tiscali.it
Delia Goletti, MD, PhD, Principal Investigator
Enrico Girardi, MD, PhD, Sub-Investigator

WHO Collaborating Center for TB and Lung Diseases, Tradate, Italy; Active, not recruiting

KNCV Tuberculosis Foundation, The Hague, Netherlands; Active, not recruiting

Centro de Diagnóstico Pneumológico, Lisbon, Portugal; Recruiting
Raquel Duarte, MD, Email: raquelafduarte@gmail.com
Raquel Duarte, MD, Principal Investigator

Clinica de Pneumologie, Marius Nasta Institute of Pneumology, Bucharest, Romania; Active, not recruiting

Department of Infectious Diseases, Suceava, Romania; Recruiting
Olga Adriana Caliman-Sturdza, MD, Email: sturdza_olga@yahoo.com
Olga Adriana Caliman-Sturdza, MD, Principal Investigator

Servei de Microbiologia, Barcelona, Spain; Recruiting
José Dominguez, MD, Email: jadominguez.igtp.germanstrias@gencat.cat
José Dominguez, MD, Principal Investigator

Karolinska Institute, Stockholm, Sweden; Recruiting
Judith Bruchfeld, MD, Email: judith.bruchfeld@karolinska.se
Judith Bruchfeld, MD, Principal Investigator
Inger Julander, MD, Sub-Investigator

Centre Antituberculeux, Hôpital Cantonal Universitarie, Geneva, Switzerland; Recruiting
Jean-Paul Janssens, MD, Email: Jean-Paul.Janssens@hcuge.ch
Jean-Paul Janssens, MD, Principal Investigator
Soccal Paola, MD, Sub-Investigator

Baþkent Üniversitesi Týp Fakültesi, Ankara, Turkey; Recruiting
Füsun Öner Eyüboðlu, MD, Email: fusune@baskent-ank.edu.tr
Füsun Öner Eyüboðlu, MD, Principal Investigator
Dilektasli Asli Gorek, MD, Sub-Investigator

Department of Chest Diseases and Tuberculosis, Ankara, Turkey; Recruiting
Oya Kayacan, MD, Email: kayacan@medicine.ankara.edu.tr
Oya Kayacan, MD, Principal Investigator
Aslýhan Yalçýn, MD, Sub-Investigator

Imperial College London, London, United Kingdom; Active, not recruiting

Chest Clinic, London, United Kingdom; Active, not recruiting

TBNET website

Starting date: June 2008
Ending date: December 2009
Last updated: January 28, 2009