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Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

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ClinicalTrials.gov Identifier: NCT03625739
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : August 15, 2018
Sponsor:
Collaborators:
Shandong University
Robert Debré Hospital
Rennes University Hospital
Information provided by (Responsible Party):
Adong Shen, Beijing Children's Hospital

Tracking Information
First Submitted Date August 8, 2018
First Posted Date August 10, 2018
Last Update Posted Date August 15, 2018
Actual Study Start Date July 1, 2018
Estimated Primary Completion Date October 1, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 8, 2018)
maximum concentration (Cmax) [ Time Frame: up to 4 weeks ]
Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: August 8, 2018)
  • time to achieve maximum concentration (Tmax) [ Time Frame: up to 4 weeks ]
    Tmax is the term used in pharmacokinetics to describe the time at which the Cmax
  • absorption rate constant (ka) [ Time Frame: up to 4 weeks ]
    Ka is the rate constant of drug absorption.
  • elimination rate constant (kel) [ Time Frame: up to 4 weeks ]
    The elimination rate constant is a value used in pharmacokinetics to describe the rate at which a drug is removed from the system.
  • half-life (t1/2) [ Time Frame: up to 4 weeks ]
    Half-life is the time required for a quantity to reduce to half its initial value.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
Official Title Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
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.
Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 18 Years
Biospecimen Retention:   Samples With DNA
Description:
whole blood and plasma
Sampling Method Non-Probability Sample
Study Population Children with anti-tuberculosis therapies.
Condition Tuberculosis
Intervention Drug: anti-tuberculosis drug
The intervention drugs are prescribed by treating caregiver
Other 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
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: August 8, 2018)
800
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2026
Estimated Primary Completion Date October 1, 2026   (Final data collection date for primary outcome measure)
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.
Sex/Gender
Sexes Eligible for Study: All
Ages up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: A-Dong Shen, Master +86-010-59616898 shenad16@hotmail.com
Listed Location Countries China
Removed Location Countries  
 
Administrative Information
NCT Number NCT03625739
Other Study ID Numbers BCH_PPK003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Responsible Party Adong Shen, Beijing Children's Hospital
Study Sponsor Beijing Children's Hospital
Collaborators
  • Shandong University
  • Robert Debré Hospital
  • Rennes University Hospital
Investigators
Principal Investigator: A-Dong Shen, Master Beijing Children's Hospital of Capital Medical University
Study Director: Yu-Jie Qi, Master Beijing Children's Hospital of Capital Medical University
Study Director: Wei Zhao, Doctor Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital
PRS Account Beijing Children's Hospital
Verification Date August 2018