Tuberculosis Clinical Trial
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
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.
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.
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Observational Model: Cohort, Time Perspective: Prospective
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