Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 800
- 试验地点
- 1
- 主要终点
- maximum concentration (Cmax)
研究概览
简要总结
This study is based on the hypothesis that the pharmacokinetics of anti-tuberculosis drugs in TB children are different from adults. The investigators aim to study the population pharmacokinetics of children receiving the anti-tuberculsis drugs for treatment of TB. In this study, the investigators will detect drug concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, the investigators also want to correlate use of anti-tuberculsis drugs with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of TB in children. It will also set the foundation for further studies to improve anti-tuberculosis drug therapies for children.
详细描述
1.Establish population pharmacokinetic (PPK) models of each anti-tuberculsis drug in children by nonlinear mixed effect modeling (NONMEM).
- At different timepoint after anti-tuberculsis drug administration, plasma samples of 100 children will be collected from neonatal intensive care unit (NICU) and pneumology department for each drug. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on .
- Plasma samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of anti-tuberculsis drug will be established by NONMEM program.
- The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error (NPDE).
2.Evaluation of the clinical feasibility and safety of individualized dosing.
- According the results of PPK models, the investigators will use dosages recommended in models to cure TB children in prospective studies. For anti-tuberculsis drug, 50 children will be collected.
- The investigators will compare the therapeutic effects and safety between children with conventional therapies and children with individualized therapies, including proportions of children with effective drug concentration, improvement speed of of children, liver and kidney functions of of children, adverse reactions of drugs and so on.
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
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children (0-18 years old) with anti-tuberculosis therapy against TB.
- •The anti-tuberculsis therapy includes drugs commonly used in children infectious diseases
- •Informed consent signed by the parents and/or guardians.
排除标准
- •Anti-tuberculosis drugs aren't involved in the therapies of children.
- •It is unable to provide complete medical records or the current condition cannot accept the study process.
- •Patients are allergic to anti-tuberculsis drugs.
- •Parents and/or guardians do not agree to participate in this study.
结局指标
主要结局
maximum concentration (Cmax)
时间窗: up to 4 weeks
Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum
次要结局
- half-life (t1/2)(up to 4 weeks)
- elimination rate constant (kel)(up to 4 weeks)
- time to achieve maximum concentration (Tmax)(up to 4 weeks)
- absorption rate constant (ka)(up to 4 weeks)
研究者
Adong Shen
Deputy Chief of China National Clinical Research Center for Respiratory Diseases
Beijing Children's Hospital