T Cell Interferon-gamma Release Assay (TIGRA) in Immunocompromised Individuals (TBNET-TIPS)
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Received Date ICMJE | June 25, 2008 | ||||||||
| Last Updated Date | December 5, 2012 | ||||||||
| Start Date ICMJE | June 2008 | ||||||||
| Primary Completion Date | May 2011 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
IGRA performance [ Time Frame: at the time of analysis ] [ Designated as safety issue: No ] performance of two IGRAs and skin test in immunocompromised patients |
||||||||
| Original Primary Outcome Measures ICMJE | Not Provided | ||||||||
| Change History | Complete list of historical versions of study NCT00707317 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE |
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 |
||||||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | T Cell Interferon-gamma Release Assay (TIGRA) in Immunocompromised Individuals | ||||||||
| Official Title ICMJE | 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:
|
||||||||
| 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 ICMJE | Observational | ||||||||
| Study Design ICMJE | 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 ICMJE |
|
||||||||
| Intervention ICMJE | Not Provided | ||||||||
| Study Group/Cohort (s) |
|
||||||||
| Publications * | Not Provided | ||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Completed | ||||||||
| Enrollment ICMJE | 1843 | ||||||||
| Completion Date | May 2011 | ||||||||
| Primary Completion Date | May 2011 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||||||
| Gender | Both | ||||||||
| Ages | 18 Years and older | ||||||||
| Accepts Healthy Volunteers | Yes | ||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||
| Location Countries ICMJE | Australia, Bulgaria, Denmark, Germany, Greece, Italy, Netherlands, Portugal, Romania, Spain, Sweden, Switzerland, Turkey, United Kingdom | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT00707317 | ||||||||
| Other Study ID Numbers ICMJE | TBNET-TIGRA | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| Responsible Party | Martina Sester, PhD, Tuberculosis Network European Trialsgroup | ||||||||
| Study Sponsor ICMJE | Tuberculosis Network European Trialsgroup | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE |
|
||||||||
| Information Provided By | Tuberculosis Network European Trialsgroup | ||||||||
| Verification Date | December 2012 | ||||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||||||