Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

Tuberculosis Clinical Trial

Official title:

Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03625739
• Other study ID #: BCH_PPK003
• Status: Recruiting
• Start date: July 1, 2018
• Est. completion date: December 31, 2026

Study information

• Verified date: August 2018
• Source: Beijing Children's Hospital
• Contact: A-Dong Shen, Master
• Phone: +86-010-59616898
• Email: shenad16[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

Description:

1.Establish population pharmacokinetic (PPK) models of each anti-tuberculsis drug in children by nonlinear mixed effect modeling (NONMEM).

1. 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 .

2. Plasma samples will be tested by high performance liquid chromatography (HPLC).

3. PPK models of anti-tuberculsis drug will be established by NONMEM program.

4. 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.

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: December 31, 2026
• Est. primary completion date: October 1, 2026
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• anti-tuberculosis drug
The intervention drugs are prescribed by treating caregiver

Locations

Country	Name	City	State
China	Beijing Children's Hospital of Capital Medical University	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Beijing Children's Hospital	Centre Hospitalier Universitaire de Rennes, Robert Debré Hospital, Shandong University

Country where clinical trial is conducted

China, 

References & Publications (3)

Ho PL, Lo PY, Chow KH, Lau EH, Lai EL, Cheng VC, Kao RY. Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. J Infect. 2010 Feb;60(2):140-5. doi: 10.1016/j.jinf.2009.11.011. Epub 2009 Dec 2. — View Citation

Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol. 2015;8(5):635-48. doi: 10.1586/17512433.2015.1060124. Epub 2015 Aug 4. Review. — View Citation

Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum concentration (Cmax)	Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum	up to 4 weeks
Secondary	time to achieve maximum concentration (Tmax)	Tmax is the term used in pharmacokinetics to describe the time at which the Cmax	up to 4 weeks
Secondary	absorption rate constant (ka)	Ka is the rate constant of drug absorption.	up to 4 weeks
Secondary	elimination rate constant (kel)	The elimination rate constant is a value used in pharmacokinetics to describe the rate at which a drug is removed from the system.	up to 4 weeks
Secondary	half-life (t1/2)	Half-life is the time required for a quantity to reduce to half its initial value.	up to 4 weeks