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Trial record 50 of 55 for:    stem cell arthritis AND stem cell transplantation

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

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ClinicalTrials.gov Identifier: NCT00707317
Recruitment Status : Completed
First Posted : June 30, 2008
Last Update Posted : December 16, 2015
Sponsor:
Information provided by (Responsible Party):
Martina Sester, PhD, Tuberculosis Network European Trialsgroup

Tracking Information
First Submitted Date June 25, 2008
First Posted Date June 30, 2008
Last Update Posted Date December 16, 2015
Study Start Date June 2008
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 5, 2012)
IGRA performance [ Time Frame: at the time of analysis ]
performance of two IGRAs and skin test in immunocompromised patients
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00707317 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: December 5, 2012)
active tuberculosis on follow-up [ Time Frame: variable follow-up on all patients ]
Active TB on follow-up depending on test result
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title T Cell Interferon-gamma Release Assay (TIGRA) in Immunocompromised Individuals
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
Brief 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.
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Plasma supernatants of stimulated samples for cytokine analysis.
Sampling Method Non-Probability Sample
Study Population immunocompetent and immunocompromised patients
Condition
  • Tuberculosis
  • Monitoring, Immunologic
Intervention Not Provided
Study 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: December 5, 2012)
1843
Original Estimated Enrollment
 (submitted: June 27, 2008)
1800
Actual Study Completion Date May 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Australia,   Bulgaria,   Denmark,   Germany,   Greece,   Italy,   Netherlands,   Portugal,   Romania,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT00707317
Other Study ID Numbers TBNET-TIGRA
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Martina Sester, PhD, Tuberculosis Network European Trialsgroup
Study Sponsor Tuberculosis Network European Trialsgroup
Collaborators Not Provided
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
PRS Account Tuberculosis Network European Trialsgroup
Verification Date December 2015