Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

NCT ID: NCT03625739

Last Updated: 2018-08-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 800 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2026-12-31

Brief 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.

Detailed 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.

Conditions

Tuberculosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

anti-tuberculosis drug

The intervention drugs are prescribed by treating caregiver

Intervention Type: DRUG

Other Intervention Names

Isoniazid; Rifampicin; Pyrazinamide; Ethambutol; Levofloxacin; Moxifloxacin; Gatifloxacin; Amikacin; Capreomycin; Kanamycin (Streptomycin); Ethionamide; Cycloserine; terizidone; Clofazimine; Bedaquiline; Delamanid; p-aminosalicylic acid; Imipenem-cilastatind; Amoxicillin-clavulanate; Thioacetazone

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shandong University

OTHER

Sponsor Role: collaborator

Hopital Universitaire Robert-Debre

OTHER

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: collaborator

Beijing Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Adong Shen

Deputy Chief of China National Clinical Research Center for Respiratory Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

A-Dong Shen, Master

Role: PRINCIPAL_INVESTIGATOR

Beijing Children's Hospital of Capital Medical University

Yu-Jie Qi, Master

Role: STUDY_DIRECTOR

Beijing Children's Hospital of Capital Medical University

Wei Zhao, Doctor

Role: STUDY_DIRECTOR

Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital

Locations

Beijing Children's Hospital of Capital Medical University

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

A-Dong Shen, Master

Role: CONTACT

shenad16@hotmail.com

+86-010-59616898

Facility Contacts

Adong Shen, Master

Role: primary

shenad16@hotmail.com

13370115087

References

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.

Reference Type: BACKGROUND

PMID: 26289222 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19961873 (View on PubMed)

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. doi: 10.1056/NEJMra035092. No abstract available.

Reference Type: BACKGROUND

PMID: 13679531 (View on PubMed)

Other Identifiers

BCH_PPK003

Identifier Type: -

Identifier Source: org_study_id