Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01252992 |
| Other study ID # |
P081253 |
| Secondary ID |
2010-A00375-34 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 14, 2011 |
| Est. completion date |
February 21, 2018 |
Study information
| Verified date |
May 2021 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Tuberculous paradoxical reactions (PR) are immune reactions occurring during the course of
antituberculous treatment and leading to a worsening of tuberculous symptoms after an initial
improvement. This phenomenon has very extensively studied in HIV infected patients where it
corresponds to the so called IRIS (immune reconstitution syndrome). However, it laso occurs
in non immuno-compromized patients, especially those with extra-pulmonary localization of
tuberculosis. The aim of the study is to look for risk factors of paradoxical reaction in non
immuno-compromized patients with extra-pulmonary tuberculosis. The investigators will
consider clinical, radiological and biological variables, including specific immune and
genetic markers. Our secondary goals are to estimate the incidence of PR, describe their
natural history; characterize the type of immune response they correspond to, and look for
better diagnostic tools.The immunological characterization and the finding of predictive
factors of PR, especially the genetic ones will allow a better understanding of biological
mechanisms that lead to their occurrence during extra-pulmonary tuberculosis treatment. The
establishment of predictive criteria could permit a better surveillance of at risk patients
for a rapid treatment, or even a prevention of PR. The establishment of new diagnostic
criteria at the time of PR could avoid numerous invasive diagnostic procedures, surgery
and/or useless prolongation of antibiotic treatment.
Description:
Primary objective :
Search for predictive factors of tuberculous paradoxical reaction (PR), with assessment of
clinical, radiological and biological factors.
Secondary objectives :
- Descriptive study of PR : incidence, clinical and radiological presentation, clinical
course ; characterization of mycobacteria strains- Search for genetic predictive factors
of PR
- Characterization of the specific immune antigene response during PR et analysis of
different cell subsets implicated in peripheral blood and locally- Characterization of
the anti-bacterial immune response before and after antituberculous treatment
- Preliminary search for new diagnosis criteria including clinical, biological (immune and
genetic) and radiological factors.Methodology : Multicentric cohort study for a total of
5 years (4 years of enrolment and one year of follow-up, with biological collection for
scientific purpose
Inclusion Status of patients (determined by a validation comity at M6)
- PR+ : PR with clinical symptoms
- rPR : pure radiological PR
- PR- : absence of RP after 6 months of treatment Development of the study
Primary outcome :
- Association between PR+ occurrence and clinical, biological and radiological factors
harvested at the diagnosis of tuberculosis..
Secondary outcomes :
- Association between PR+ and rPR
- occurrence and the above quoted factors.- Descriptive study : clinical, biological, and
radiological presentation of PR+ and rPR, characterization of isolated BK strains in PR+
patients
- Immunological study in 20 PR+ patients and 20 RP- : 20 patients per group will allow a
80% power to detect, by means of bilateral Mann-Whitney test with alpha=5%, any
difference in the count of specific cells corresponding to at least one standard
deviation of the primary immunological outcome
- controls: variation between tuberculosis diagnostic and either PR time or M2 (in absence
of PR), of the specific cells, macrophages, dendritic cells, gamma-delta lymphocytes, NK
et CD4 cells counts
- Preliminary search for diagnostic criteria that can be used at the time of PR
occurrence: variation between D0 and the PR of clinical, biological, radiological
immunological et genomic of PR+ patients.
- Evolution specific and non specific immune response of mycobacterial antigen at
tuberculosis diagnosis during tuberculosis treatment and after. Sample size calculation
- prognostic study : Patients will be recruited and followed until the achievement of a 20
PR+ sample. The investigators will have to analyze 200 patients.
