New Genomic Techniques and Management of Multidrug-resistant Tuberculosis

NCT ID: NCT04397536

Last Updated: 2022-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

172 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-29

Study Completion Date

2022-12-01

Brief Summary

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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

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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

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Multi-Drug Resistant Tuberculosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort

Patients diagnosed with MDR-TB

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* Patient with non MDR tuberculosis ;
* Impossibility of carrying out a phenotypic antibiogram (absence of bacterial culture, contaminated culture)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexandra AUBRY, Pr

Role: PRINCIPAL_INVESTIGATOR

Pitié-Salpêtrière Hospital (AP-HP)

Locations

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Pitié Salpêtrière Hospital

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Alexandra AUBRY, Pr

Role: CONTACT

01 42 16 20 70

Facility Contacts

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Alexandra AUBRY, Pr

Role: primary

01 42 16 20 70

Wladimir SOUGAKOFF, Dr

Role: backup

01 42 16 20 70

Other Identifiers

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APHP190613

Identifier Type: -

Identifier Source: org_study_id

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