Multi-site Cohort Study for the Development of Personalized Pharmacotherapy in Patients With Tuberculosis (TB)

Study Overview
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Brief Summary
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Based on the collected antibiotic concentration data and individual patient's clinical information, a pharmacokinetic analysis report that can be applied for dose adjustment of the individual patient is provided. The pharmacokinetic/pharmacodynamic index using the minimum inhibition concentration (MIC) of the antibiotic obtained from the patient's clinical isolate is also explored. Utilizing these, we intend to establish a population pharmacokinetic model of antibiotics prescribed in treating Tuberculosis and Nontuberculous mycobacteria (NTM). The developed population pharmacokinetic model can be applied for therapeutic drug monitoring (TDM) based on dose adjustment through the obtained pharmacokinetic parameters.

Official Title
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Multi-site Cohort Study for the Development of Personalized Pharmacotherapy in Patients With Tuberculosis (TB)

Conditions
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Tuberculosis, Latent Tuberculosis, Nontuberculous Mycobacterium Infection

Intervention / Treatment
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* Procedure: therapeutic drug monitoring(TDM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with Tuberculosis. Latent tuberculosis, or Nontuberculous mycobacteria (NTM) disease and currently under treatment with antibiotic drugs. Patients who understand and voluntarily sign an informed consent form before any study-related procedures are conducted. Exclusion Criteria: - Children (minors) for whom the consent of a legal representative is impossible.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: therapeutic drug monitoring(TDM)|Based on this data, population pharmacokinetic models of antibiotics drugs that can be applicable to TDM will be developed.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum plasma concentration (Cmax) |  | Around 2 weeks or later after the first administration of antibiotics | 
| Area under the plasma concentration versus time curve (AUC) |  | Around 2 weeks or later after the first administration of antibiotics | 
| Development of population pharmacokinetic (PK) model of antibiotics | The population pharmacokinetic properties of anti-TB drugs will be identified by plasma drug concentrations, pharmacogenomics genotypes, or clinical information. Population pharmacokinetic analysis will be performed by using NONMEN Ⅶ software. (ICON development solutions, Ellicott city, Maryland, USA) | Through study completion, an average 3 years | 
| AUC/MIC | If MIC data is available. | Through study completion, an average 3 years | 
| Cmax/MIC | If MIC data is available. | Through study completion, an average 3 years | 
| Time above MIC (T > MIC) | If MIC data is available. | Through study completion, an average 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| N-acetyltransferase 2(NAT2) Pharmacogenetic analysis | The six single nucleotide polymorphism (SNP) of NAT2, i.e., genotypes: rs1801279 for 191G>A, rs1041983 for 282C>T, rs1801280 341T>C, rs1799930 for 590G>A, rs1208 for 803A>G, and rs1799931 for 857G>A, will be analyzed with SNaPshot® kit (measurement tool) and categorized phenotypes of patients into rapid, intermediate, and slow acetylator. | baseline, pre-procedure | 
| Solute carrier organic anion transporter family member 1B1(SLCO1B1) Pharmacogenetic analysis | The two SNP of SLCO1B1, i.e., genotypes: rs2306283, rs4149056, will be analyzed with SNaPshot® kit and categorized phenotypes of patients into normal, intermediate, low transporter function. | baseline, pre-procedure | 
| Biomarker exploration for adverse drug reaction |  | Through study completion, an average 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NTM, TB, Latent Tuberculosis Infection (LTBI)