Impact of New Genomic Tools on the Management of Patients With Multidrug-resistant Tuberculosis
试验速览
- 阶段
- 不适用
- 入组人数
- 172
- 试验地点
- 1
- 主要终点
- Sensitivity for the detection of bedaquiline resistance
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Patient with non MDR tuberculosis ;
- •Impossibility of carrying out a phenotypic antibiogram (absence of bacterial culture, contaminated culture)
结局指标
主要结局
Sensitivity for the detection of bedaquiline resistance
时间窗: At the end enrollment
The sensitivity of WGS-based strategies will be compared to phenotypic strategy for the detection of bedaquiline's resistance
次要结局
- Number of laboratory procedures(At the end enrollment)
- Costs of personal time and laboratory procedures(At the end enrollment)
- Performances (deadlines to obtain results, sensitivity, specificity) to identify the species within the tuberculosis complex, and to diagnose resistance to anti-tuberculosis drugs(At the end enrollment)
- Performances (sensitivity, specificity) of the WGS strategy by using different pipelines(At the end enrollment)
- Number of anti-tuberculosis days(At the end enrollment)