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Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03625739
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : August 15, 2018
Shandong University
Robert Debré Hospital
Rennes University Hospital
Information provided by (Responsible Party):
Adong Shen, Beijing Children's Hospital

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.

Condition or disease Intervention/treatment
Tuberculosis Drug: anti-tuberculosis drug

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 18 Years
Official Title: Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : October 1, 2026
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Intervention Details:
  • 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

Primary Outcome Measures :
  1. maximum concentration (Cmax) [ Time Frame: up to 4 weeks ]
    Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum

Secondary Outcome Measures :
  1. 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

  2. absorption rate constant (ka) [ Time Frame: up to 4 weeks ]
    Ka is the rate constant of drug absorption.

  3. 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.

  4. 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.

Biospecimen Retention:   Samples With DNA
whole blood and plasma

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Children with anti-tuberculosis therapies.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03625739

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Contact: A-Dong Shen, Master +86-010-59616898

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Beijing Children's Hospital of Capital Medical University Recruiting
Beijing, China
Contact: Adong Shen, Master    13370115087   
Sponsors and Collaborators
Beijing Children's Hospital
Shandong University
Robert Debré Hospital
Rennes University Hospital
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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
Additional Information:

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Responsible Party: Adong Shen, Deputy Chief of China National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital Identifier: NCT03625739    
Other Study ID Numbers: BCH_PPK003
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Additional relevant MeSH terms:
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Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Clavulanic Acid
Amoxicillin-Potassium Clavulanate Combination
Aminosalicylic Acid
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors