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

Recruiting

• Conditions: Latent Tuberculosis; Nontuberculous Mycobacterium Infection; Tuberculosis

• Registration Number: NCT05280886
• Lead Sponsor: Inje University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-07-24
• Study First Submitted: 2022-01-25
• Study First Submitted QC: 2022-03-06
• Study First Posted: 2022-03-15
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-18
• Last Update Posted: 2023-04-19
• Primary Completion: 2024-12-31
• Study Completion: 2025-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 5000

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The maximum plasma concentration (Cmax)	Around 2 weeks or later after the first administration of antibiotics
Development of population pharmacokinetic (PK) model of antibiotics	Through study completion, an average 3 years	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)
AUC/MIC	Through study completion, an average 3 years	If MIC data is available.
Area under the plasma concentration versus time curve (AUC)	Around 2 weeks or later after the first administration of antibiotics
Cmax/MIC	Through study completion, an average 3 years	If MIC data is available.
Time above MIC (T > MIC)	Through study completion, an average 3 years	If MIC data is available.

Secondary Outcome Measures

Name	Time	Method
Solute carrier organic anion transporter family member 1B1(SLCO1B1) Pharmacogenetic analysis	baseline, pre-procedure	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.
Biomarker exploration for adverse drug reaction	Through study completion, an average 3 years
N-acetyltransferase 2(NAT2) Pharmacogenetic analysis	baseline, pre-procedure	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.

Trial Locations

Locations (3)

General Hospital Dr. Soetomo; 🇮🇩 Surabaya, Jawa Timur, Indonesia

Ibnu Sina Hospital; 🇮🇩 Gresik, Perum Grand, Indonesia

Inje University Busan Paik Hoapital Clinical Trial Center; 🇰🇷 Busan, Korea, Republic of