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

Tuberculosis Clinical Trial

— TBNET-TIPS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00707317
• Other study ID #: TBNET-TIGRA
• Status: Completed
• Phase: N/A
• First received: June 25, 2008
• Last updated: December 15, 2015
• Start date: June 2008
• Est. completion date: May 2011

Study information

• Verified date: December 2015
• Source: Tuberculosis Network European Trialsgroup
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1843
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Monitoring, Immunologic
• Tuberculosis

Locations

Country	Name	City	State
Australia	Cellestis Limited	Carnegie
Bulgaria	National Center of Infectious and Parasitic Diseases	Sofia
Denmark	Herlev Hospital	Herlev
Germany	Research Center Borstel	Borstel
Germany	HIV Treatment and Clinical Research Unit	Frankfurt
Germany	Department of Infectious Diseases, Univ. of Freiburg	Freiburg
Germany	University of the Saarland	Homburg
Greece	Respiratory Medicine, University of Thessaly	Mezourlo-Larissa
Italy	Emerging Bacterial Pathogens Unit	Milan
Italy	National Institute for Infectious Diseases L. Spallanzani	Roma
Italy	WHO Collaborating Center for TB and Lung Diseases	Tradate
Netherlands	KNCV Tuberculosis Foundation	The Hague
Portugal	Centro de Diagnóstico Pneumológico	Lisbon
Romania	Clinica de Pneumologie, Marius Nasta Institute of Pneumology	Bucharest
Spain	Servei de Microbiologia	Barcelona
Sweden	Karolinska Institute	Stockholm
Switzerland	Centre Antituberculeux, Hôpital Cantonal Universitarie	Geneva
Turkey	Baþkent Üniversitesi Týp Fakültesi	Ankara
Turkey	Department of Chest Diseases and Tuberculosis	Ankara
United Kingdom	Chest Clinic	London
United Kingdom	Imperial College London	London

Sponsors (1)

Lead Sponsor	Collaborator
Tuberculosis Network European Trialsgroup

Countries where clinical trial is conducted

Australia,  Bulgaria,  Denmark,  Germany,  Greece,  Italy,  Netherlands,  Portugal,  Romania,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (2)

Lange C, van Leth F, Sester M; TBnet. Viral Load and Risk of Tuberculosis in HIV Infection. J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):e51-3. doi: 10.1097/QAI.0000000000000834. — View Citation

Sester M, van Leth F, Bruchfeld J, Bumbacea D, Cirillo DM, Dilektasli AG, Domínguez J, Duarte R, Ernst M, Eyuboglu FO, Gerogianni I, Girardi E, Goletti D, Janssens JP, Julander I, Lange B, Latorre I, Losi M, Markova R, Matteelli A, Milburn H, Ravn P, Scho — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IGRA performance	performance of two IGRAs and skin test in immunocompromised patients	at the time of analysis	No
Secondary	active tuberculosis on follow-up	Active TB on follow-up depending on test result	variable follow-up on all patients	No

External Links

•   TBNET website