Multi-Drug Resistant TuberculosisGENO-MDRNCT04397536
New Genomic Techniques and Management of Multidrug-resistant Tuberculosis
An observational study of Multi-Drug Resistant Tuberculosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
In the context of the emergence of cases of multidrug-resistant tuberculosis (MDR-TB) it is crucial to improve patient's management. Therefore, assessing the place of innovative strategies enabling the diagnosis of those cases (e.g. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multi-Drug Resistant Tuberculosis
- How many people
- 172 participants
- Where
- 1 siteFrance
- Study dates
- 29 Aug 2020to 1 Dec 2022
- 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: All the patients diagnosed with MDR-TB in France during the frame time of the project
Who may be able to join
- age ≥ 18 years ;
- patient with bacteriologically proven tuberculosis due to a multidrug resistance strain (i.e. resistant to rifampin and isoniazid)
- patient informed of the study and not opposed to participating in the research
Who cannot join
- Patient with non MDR tuberculosis ;
- Impossibility of carrying out a phenotypic antibiogram (absence of bacterial culture, contaminated culture)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Pitié Salpêtrière Hospital
Paris, 75013
Alexandra AUBRY, Pr, 01 42 16 20 70, alexandra.aubry@aphp.fr
Wladimir SOUGAKOFF, Dr, 01 42 16 20 70, wladimir.sougakoff@sorbonne-universite.fr
About this study
Official title: Impact of New Genomic Tools on the Management of Patients With Multidrug-resistant Tuberculosis
In the context of the emergence of cases of multidrug-resistant tuberculosis (MDR-TB) it is crucial to improve patient's management. Therefore, assessing the place of innovative strategies enabling the diagnosis of those cases (e.g. WGS and Deeplex-MycTB) in the personalized care of patients with MDR-TB and the rationalization of medical biology procedures is a major issue. This project participates to these goals since the investigators will : (i) assess the diagnostic qualities and the performance of the different innovatives strategies enabling detection of resistance to anti-tuberculosis drugs, (ii) assess the impact of these strategies in the implementation of personalized treatments for MDR-TB patients, and (iii) assess the overall costs of these strategies.
Read the detailed description
Non-interventional monocentric study on the evaluation of the reliability and validity of a diagnostic test based on a biological collection of M. tuberculosis MDR strains received at the NRC-MyRMA. The study will apply to all strains and samples of multidrug-resistant M. tuberculosis detected in France. These strains are all sent to NRC-MyRMA (National Reference Center for Mycobacteria and resistance to anti-tuberculosis drugs) for Drug Susceptibility testing (DST) to first and second line anti-tuberculosis drugs in accordance with the national guidelines.
Currently, a genotypic and phenotypic diagnosis of antibiotic resistance is carried out upon receipt of a strain of M. tuberculosis MDR at CNR-MyRMA, respectively by PCR-sequence techniques and commercial kits and by phenotypic antibiogram by the method of reference called proportions. In the case of a sample, only the genotypic diagnosis is immediately feasible, the realization of the phenotypic diagnosis can only be carried out from a strain, so the investigators must wait for a positive culture to be obtained.
In addition to this current strategy, two innovative strategies based on the sequencing of the complete genome of the strains (WGS and Deeplex-MycTB) will be implemented. These analyzes will not require an additional patient's samples.
The sensitivities and specificities and the area under the ROC curve of the different tests, with respect to each resistance, will be calculated and their confidence interval will be estimated by bootstrap. The comparison of the sensitivities, specificities and areas under the curve between the different techniques will be carried out by a Gaussian test based on a bootstrap. The agreement between the different tests will be measured by calculating a Cohen kappa. A Kappa confidence interval will be estimated by bootstrap. The Kappa between each genotypic method and the phenotypic method will be compared by a Gaussian test based on a bootstrap.
The comparison of the results reporting times will be done by a comparison test of the symmetry of the rows with respect to the median value (Mann Whithney Wilcoxon test.
In general, the quantitative variables will be described by the classic position measurements (mean, median, 1st and 3rd quartile, minimum and maximum) and dispersion measures (standard deviation). Qualitative variables will be described in terms of absolute value and percentage.
Degree of statistical significance:
The significance level for the tests will be set for an alpha of 0.05.
Software:
All analyzes will be done at the URC on SAS software or R software in their latest version available at the time they are performed.
- Conditions
- Multi-Drug Resistant Tuberculosis
- Keywords
- Tuberculosis, Multi-Drug Resistance, Diagnosis, Whole Genome
- Medical subject headings
- Tuberculosis, Multidrug-Resistant, Tuberculosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort | Patients diagnosed with MDR-TB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity for the detection of bedaquiline resistance
The sensitivity of WGS-based strategies will be compared to phenotypic strategy for the detection of bedaquiline's resistance
Measured: At the end enrollment
Secondary outcomes (5)
Performances (deadlines to obtain results, sensitivity, specificity) to identify the species within the tuberculosis complex, and to diagnose resistance to anti-tuberculosis drugs
Comparison of the performances (deadlines to obtain results, sensitivity, specificity) of WGS and Deeplex-MycTB strategies compared to the performances of the phenotypic reference method, to identify the species within the tuberculosis complex, and to diagnose resistance to anti-tuberculosis drugs from bacterial cultures and directly from positive samples on microscopic examination
Measured: At the end enrollment
Number of anti-tuberculosis days
Comparison of the number of anti-tuberculosis days that would have been prescribed by excess or by error between the date when the genotypic drug susceptibility testing results are available and the reception of the sample or strain for each of the strategies, and the date when the final drug susceptibility results are available (i.e. those obtained with the phenotypic method which is the reference method)
Measured: At the end enrollment
Performances (sensitivity, specificity) of the WGS strategy by using different pipelines
The sensitivity and the specificity of the WGS results analysed with different pipeline ((BioNumerics, TB-Profiler, PhyResSe) as well as CNR-MyrMA own pipeline) will be compared to the drug susceptibility testing result of the phenotypic method, which is the reference method
Measured: At the end enrollment
Number of laboratory procedures
Number of laboratory procedures performed for WGS and Deeplex-MycTB strategies compared to the number of procedures performed for the current genotypic strategy used at the CNR-MyrMA
Measured: At the end enrollment
Costs of personal time and laboratory procedures
Costs of personal time (medical and non-medical) and laboratory procedures required for WGS and Deeplex-MycTB strategies compared to costs of personal time and laboratory procedures required for the genotypic methods used at CNR-MyrMA
Measured: At the end enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2020
- Study start29 Aug 2020
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multi-Drug Resistant 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 172 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandra AUBRY, Pr, Principal investigator, Pitié-Salpêtrière Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04397536
- Sponsor's protocol ID
- APHP190613
- Acronym
- GENO-MDR
- Status last verified
- Mar 2022
- First submitted
- 12 May 2020
- Last updated
- 29 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of New Genomic Tools on the Management of Patients With Multidrug-resistant Tuberculosis
- ClinicalTrials.gov ID
- NCT04397536
- Acronym / sponsor ID
- GENO-MDR / APHP190613
- Conditions
- Multi-Drug Resistant Tuberculosis
- Keywords
- Tuberculosis, Multi-Drug Resistance, Diagnosis, Whole Genome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 172 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 29 Aug 2020 (actual)
- Primary completion
- 1 Sep 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 21 May 2020 (actual)
- 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.
In the context of the emergence of cases of multidrug-resistant tuberculosis (MDR-TB) it is crucial to improve patient's management. Therefore, assessing the place of innovative strategies enabling the diagnosis of those cases (e.g. WGS and Deeplex-MycTB) in the personalized care of patients with MDR-TB and the rationalization of medical biology procedures is a major issue. This project participates to these goals since the investigators will : (i) assess the diagnostic qualities and the performance of the different innovatives strategies enabling detection of resistance to anti-tuberculosis drugs, (ii) assess the impact of these strategies in the implementation of personalized treatments for MDR-TB patients, and (iii) assess the overall costs of these strategies.
Detailed description
Non-interventional monocentric study on the evaluation of the reliability and validity of a diagnostic test based on a biological collection of M. tuberculosis MDR strains received at the NRC-MyRMA. The study will apply to all strains and samples of multidrug-resistant M. tuberculosis detected in France. These strains are all sent to NRC-MyRMA (National Reference Center for Mycobacteria and resistance to anti-tuberculosis drugs) for Drug Susceptibility testing (DST) to first and second line anti-tuberculosis drugs in accordance with the national guidelines.
Currently, a genotypic and phenotypic diagnosis of antibiotic resistance is carried out upon receipt of a strain of M. tuberculosis MDR at CNR-MyRMA, respectively by PCR-sequence techniques and commercial kits and by phenotypic antibiogram by the method of reference called proportions. In the case of a sample, only the genotypic diagnosis is immediately feasible, the realization of the phenotypic diagnosis can only be carried out from a strain, so the investigators must wait for a positive culture to be obtained.
In addition to this current strategy, two innovative strategies based on the sequencing of the complete genome of the strains (WGS and Deeplex-MycTB) will be implemented. These analyzes will not require an additional patient's samples.
The sensitivities and specificities and the area under the ROC curve of the different tests, with respect to each resistance, will be calculated and their confidence interval will be estimated by bootstrap. The comparison of the sensitivities, specificities and areas under the curve between the different techniques will be carried out by a Gaussian test based on a bootstrap. The agreement between the different tests will be measured by calculating a Cohen kappa. A Kappa confidence interval will be estimated by bootstrap. The Kappa between each genotypic method and the phenotypic method will be compared by a Gaussian test based on a bootstrap.
The comparison of the results reporting times will be done by a comparison test of the symmetry of the rows with respect to the median value (Mann Whithney Wilcoxon test.
In general, the quantitative variables will be described by the classic position measurements (mean, median, 1st and 3rd quartile, minimum and maximum) and dispersion measures (standard deviation). Qualitative variables will be described in terms of absolute value and percentage.
Degree of statistical significance:
The significance level for the tests will be set for an alpha of 0.05.
Software:
All analyzes will be done at the URC on SAS software or R software in their latest version available at the time they are performed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort | – | –Patients diagnosed with MDR-TB |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All the patients diagnosed with MDR-TB in France during the frame time of the project
Key inclusion criteria (3 listed)
- age ≥ 18 years ;
- patient with bacteriologically proven tuberculosis due to a multidrug resistance strain (i.e. resistant to rifampin and isoniazid)
- patient informed of the study and not opposed to participating in the research
Key exclusion criteria (2 listed)
- Patient with non MDR tuberculosis ;
- Impossibility of carrying out a phenotypic antibiogram (absence of bacterial culture, contaminated culture)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Sensitivity for the detection of bedaquiline resistance
Time frame: At the end enrollment
The sensitivity of WGS-based strategies will be compared to phenotypic strategy for the detection of bedaquiline's resistance
5 secondary outcomes
Performances (deadlines to obtain results, sensitivity, specificity) to identify the species within the tuberculosis complex, and to diagnose resistance to anti-tuberculosis drugs
Time frame: At the end enrollment
Number of anti-tuberculosis days
Time frame: At the end enrollment
Performances (sensitivity, specificity) of the WGS strategy by using different pipelines
Time frame: At the end enrollment
Number of laboratory procedures
Time frame: At the end enrollment
Costs of personal time and laboratory procedures
Time frame: At the end enrollment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2022.
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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.
Alexandra AUBRY, Pr principal investigator
Pitié-Salpêtrière Hospital
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 Multi-Drug Resistant 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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 29 Mar 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alexandra AUBRY, Pr (01 42 16 20 70, alexandra.aubry@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity for the detection of bedaquiline resistance (time frame: At the end enrollment). 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 29 Mar 2022.