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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Martina Sester, PhD, Tuberculosis Network European Trialsgroup
ClinicalTrials.gov Identifier:
NCT00707317
First received: June 25, 2008
Last updated: December 5, 2012
Last verified: December 2012
  Purpose

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.

Condition
Tuberculosis
Monitoring, Immunologic

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Tuberculosis Network European Trialsgroup:

Primary Outcome Measures:
  • IGRA performance [ Time Frame: at the time of analysis ] [ Designated as safety issue: No ]
    performance of two IGRAs and skin test in immunocompromised patients


Secondary Outcome Measures:
  • active tuberculosis on follow-up [ Time Frame: variable follow-up on all patients ] [ Designated as safety issue: No ]
    Active TB on follow-up depending on test result


Biospecimen Retention:   Samples Without DNA

Plasma supernatants of stimulated samples for cytokine analysis.


Enrollment: 1843
Study Start Date: June 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
HIV infected individuals
2
patients with chronic renal failure
3
patients after solid organ transplantation (lung, liver, kidney, kidney-pancreas)
4
patients with rheumatoid arthritis
5
stem cell transplant recipients
6
immunocompromised patients with confirmed tuberculosis
7
immunocompetent controls with no known risk of exposure or tuberculosis

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

immunocompetent and immunocompromised patients

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707317

Locations
Australia
Cellestis Limited
Carnegie, Australia
Bulgaria
National Center of Infectious and Parasitic Diseases
Sofia, Bulgaria
Denmark
Herlev Hospital
Herlev, Denmark
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, Germany
Greece
Respiratory Medicine, University of Thessaly
Mezourlo-Larissa, Greece
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, Italy
Netherlands
KNCV Tuberculosis Foundation
The Hague, Netherlands
Portugal
Centro de Diagnóstico Pneumológico
Lisbon, Portugal
Romania
Clinica de Pneumologie, Marius Nasta Institute of Pneumology
Bucharest, Romania
Spain
Servei de Microbiologia
Barcelona, Spain
Sweden
Karolinska Institute
Stockholm, Sweden
Switzerland
Centre Antituberculeux, Hôpital Cantonal Universitarie
Geneva, Switzerland
Turkey
Department of Chest Diseases and Tuberculosis
Ankara, Turkey
Baþkent Üniversitesi Týp Fakültesi
Ankara, Turkey
United Kingdom
Imperial College London
London, United Kingdom
Chest Clinic
London, United Kingdom
Sponsors and Collaborators
Tuberculosis Network European Trialsgroup
Investigators
Principal Investigator: Martina Sester, PhD Department of Transplant and Infection Immunology, University of the Saarland, 66421 Homburg
Study Chair: Christoph Lange, MD, PhD Div. of Clinical Infectious Diseases, Medical Clinic, Research Center Borstel, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: Martina Sester, PhD, Professor, Tuberculosis Network European Trialsgroup
ClinicalTrials.gov Identifier: NCT00707317     History of Changes
Other Study ID Numbers: TBNET-TIGRA
Study First Received: June 25, 2008
Last Updated: December 5, 2012
Health Authority: Germany: Ethics Commission

Keywords provided by Tuberculosis Network European Trialsgroup:
M. tuberculosis
latent tuberculosis infection
Quantiferon assay
ELISPOT assay
tuberculin skin test
immunocompromised patients

Additional relevant MeSH terms:
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections

ClinicalTrials.gov processed this record on October 29, 2014