Extrapulmonary TuberculosisPARATBNCT01252992
Paradoxical Reactions in Non Immuno-compromized Patients With Extrapulmonary Tuberculosis
An observational study of Extrapulmonary Tuberculosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extrapulmonary Tuberculosis
- What is being tested?
- Genetic analysis, Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM and Immunologic analysis
- Type of treatment
- Surgery or procedure
- How many people
- 135 participants
- Where
- 1 siteFrance
- Study dates
- 14 Mar 2011to 21 Feb 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Extra-pulmonary tuberculosis
Who may be able to join
- Extrapulmonary tuberculosis, with associated pulmonary localization or not
- Treatment started less than 5 days ago
- Negative HIV serology
- Social insurance
- Age >= 18- Foreseeable follow-up of at last one year
- Signed Free Inform Consent
Who cannot join
- HIV infection
- immuno-suppressive treatment (including corticosteroids > 10 mg /d prednisone equivalent, however patients with corticotherapy could be included during the phase 2 of the study)
- central neurological system tuberculosis and tuberculous pericarditis - pure pulmonary tuberculosis
- multiresistant tuberculosis
- pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Paradoxical Reactions During Anti-mycobacterial Treatment of Extrapulmonary Tuberculosis in Non Immuno-compromized Patients : Clinical, Radiological et Immunological
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.
Read the detailed 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.
- Conditions
- Extrapulmonary Tuberculosis
- Being tested
- Genetic analysis, Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM, Immunologic analysis, QuantiferonTB Gold test
- Keywords
- Extrapulmonary, Tuberculosis, Paradoxical reaction, Risk factors, Incidence, CT scan, Natural history, Immune system phenomena, Immune markers, Gene Expression Profiling
- Medical subject headings
- Tuberculosis, Extrapulmonary, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic analysisGenetic
- identification of candidates genes by a differential analysis of the whole transcriptome of the peripheral leucocytes of 20 PR+ patients and 20 RP- controls, at D0, D15, M2,;
- Genetic association analysis: comparison of allelic distributions of SNPs (diallelic markers) within the candidate genes, between PR+ and PR- patients, in the whole cohort.
One supplementary ACD tube of 5 ml à D0, D15, M2, PR+, for RNA extraction.
Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRMRadiation
at day 0, Month 2, paradoxical reaction, end of treatment, read by an independent radiologist
Immunologic analysisOther
For patients included until 20 PR+ : blood puncture of 4 ACD tubes of 10 ml, 1 EDTA tube of 7,5 ml et 1 heparinate lithium tube of 7,5ml at D0, D15, M2, and M6 and at the time of an potential RP+
QuantiferonTB Gold testOther
at M0, M2, M6 and in case of PR+.
| Study group | Role | What they receive |
|---|---|---|
| 1:paradoxical reaction negative (RP-) | control group with tuberculosis but without paradoxical reaction Receives: Genetic: Genetic analysis; Radiation: Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM; Other: Immunologic analysis | |
| 1:paradoxical reaction negative (RP+) | group with tuberculosis and paradoxical reaction Receives: Genetic: Genetic analysis; Radiation: Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM; Other: Immunologic analysis; Other: QuantiferonTB Gold test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Risk factors of paradoxical reaction
Risk factors of paradoxical reaction : clinical, radiological immune and genetic factors
Measured: at 6 months
Secondary outcomes (3)
Incidence and natural history of paradoxical reactions
Measured: during the first 6 months
Immune description of paradoxical reactions
Measured: during the first 6 months
Preliminary study of Diagnosis factors of paradoxical reaction
Measured: during the first 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2010 (estimated)
- Study start14 Mar 2011
- Primary completion21 Feb 2018
- Study completion21 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extrapulmonary TuberculosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne BOURGARIT, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01252992
- Sponsor's protocol ID
- P081253
- Other IDs
- 2010-A00375-34
- Acronym
- PARATB
- Status last verified
- May 2021
- First submitted
- 27 Nov 2010
- Last updated
- 28 May 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paradoxical Reactions During Anti-mycobacterial Treatment of Extrapulmonary Tuberculosis in Non Immuno-compromized Patients : Clinical, Radiological et Immunological
- ClinicalTrials.gov ID
- NCT01252992
- Acronym / sponsor ID
- PARATB / P081253
- Conditions
- Extrapulmonary Tuberculosis
- Keywords
- Extrapulmonary, Tuberculosis, Paradoxical reaction, Risk factors, Incidence, CT scan, Natural history, Immune system phenomena
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 14 Mar 2011 (actual)
- Primary completion
- 21 Feb 2018 (actual)
- Study completion
- 21 Feb 2018 (actual)
- First posted
- 3 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1:paradoxical reaction negative (RP-) | – | Genetic: Genetic analysis, Radiation: Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM, Other: Immunologic analysiscontrol group with tuberculosis but without paradoxical reaction |
| 1:paradoxical reaction negative (RP+) | – | Genetic: Genetic analysis, Radiation: Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM, Other: Immunologic analysis, Other: QuantiferonTB Gold testgroup with tuberculosis and paradoxical reaction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Extra-pulmonary tuberculosis
Key inclusion criteria (6 listed)
- Extrapulmonary tuberculosis, with associated pulmonary localization or not
- Treatment started less than 5 days ago
- Negative HIV serology
- Social insurance
- Age >= 18- Foreseeable follow-up of at last one year
Key exclusion criteria (5 listed)
- HIV infection
- immuno-suppressive treatment (including corticosteroids > 10 mg /d prednisone equivalent, however patients with corticotherapy could be included during the phase 2 of the study)
- central neurological system tuberculosis and tuberculous pericarditis - pure pulmonary tuberculosis
- multiresistant tuberculosis
- pregnancy or breast feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genetic analysis1. identification of candidates genes by a differential analysis of the whole transcriptome of the peripheral leucocytes of 20 PR+ patients and 20 RP- controls, at D0, D15, M2,; 2. Genetic association analysis: comparison of allelic distributions of SNPs (diallelic markers) within the candidate genes, between PR+ and PR- patients, in the whole cohort. One supplementary ACD tube of 5 ml à D0, D15, M2, PR+, for RNA extraction. | Genetic | 1:paradoxical reaction negative (RP+), 1:paradoxical reaction negative (RP-) |
| Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRMat day 0, Month 2, paradoxical reaction, end of treatment, read by an independent radiologist | Radiation | 1:paradoxical reaction negative (RP+), 1:paradoxical reaction negative (RP-) |
| Immunologic analysisFor patients included until 20 PR+ : blood puncture of 4 ACD tubes of 10 ml, 1 EDTA tube of 7,5 ml et 1 heparinate lithium tube of 7,5ml at D0, D15, M2, and M6 and at the time of an potential RP+ | Other | 1:paradoxical reaction negative (RP+), 1:paradoxical reaction negative (RP-) |
| QuantiferonTB Gold testat M0, M2, M6 and in case of PR+. | Other | 1:paradoxical reaction negative (RP+) |
Primary outcome
Risk factors of paradoxical reaction
Time frame: at 6 months
Risk factors of paradoxical reaction : clinical, radiological immune and genetic factors
3 secondary outcomes
Incidence and natural history of paradoxical reactions
Time frame: during the first 6 months
Immune description of paradoxical reactions
Time frame: during the first 6 months
Preliminary study of Diagnosis factors of paradoxical reaction
Time frame: during the first 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne BOURGARIT, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Extrapulmonary Tuberculosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Risk factors of paradoxical reaction (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2021.