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Population Pharmacokinetics of Meropenem and Linezolid in Children With Severe Infectious Diseases

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ClinicalTrials.gov Identifier: NCT03643497
Recruitment Status : Recruiting
First Posted : August 22, 2018
Last Update Posted : August 23, 2018
Sponsor:
Collaborators:
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 meropenem and linezolid in severe infectious children are different from mild infectious children and adults. The investigators aim to study the population pharmacokinetics of children receiving the meropenem and linezolid for treatment of severe infectious diseases. In this study, the investigators will detect drug concentration in plasma and cerebrospinal fluid by using residual blood samples of blood and cerebrospinal fluid gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, the investigators also want to correlate use of meropenem and linezolid with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of severe infectious diseases in children. It will also set the foundation for further studies to improve anti- infective drug therapies for severe infectious children.

Condition or disease Intervention/treatment
Children;Infection Drug: anti-infective drugs

Detailed Description:

1.Establish population pharmacokinetic (PPK) models of meropenem and linezolid in severe infectious children by nonlinear mixed effect modeling (NONMEM).

  1. At different time point after meropenem or linezolid administration, plasma and/or cerebrospinal fluid samples of 100 children will be collected from pediatric intensive care unit (PICU) for each drug. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on.
  2. Plasma and cerebrospinal fluid samples will be tested by high performance liquid chromatography (HPLC).
  3. PPK models of meropenem and linezolid 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 severe infectious children in prospective studies. For antibiotic 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 in severe infectious diseases, including proportions of children with effective drug concentration, improvement speed of children, liver and kidney functions 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 Meropenem and Linezolid in Children With Severe Infectious Diseases
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Children with the usage of anti-infective drugs
Children received meropenem or linezolid monotherapy in the treatment of seven infectious diseases
Drug: anti-infective drugs
According to the models of population pharmacokinetics, the investigators and want to correlate use of antibiotics with treatment effectiveness and safety in children
Other Names:
  • meropenem
  • linezolid




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 concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose


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 is observed

  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 and cerebrospinal fluid


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Severe infectious children with anti-infectious therapies
Criteria

Inclusion Criteria:

  • Children (0-18 years old) with anti-infective therapy against severe infectious diseases.
  • The anti-infective therapy includes meropenem and linezolid commonly used in children with infectious diseases,
  • Children severe infectious diseases include severe pneumonia, sepsis, purulent meningitis and other diseases with severe infection.
  • Informed consent signed by the parents and/or guardians

Exclusion Criteria:

  • Anti-infective 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 meropenem or linezolid.
  • 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 ClinicalTrials.gov identifier (NCT number): NCT03643497


Contacts
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Contact: Shen A-Dong, Master 010-59616898 shenad16@hotmail.com

Locations
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China
Beijing Children's Hospital of Capital Medical University Recruiting
Beijing, China
Contact: Adong Shen, Master    13370115087    shenad16@hotmail.com   
Sponsors and Collaborators
Beijing Children's Hospital
Shandong University
Robert Debré Hospital
Rennes University Hospital
Investigators
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Principal Investigator: Shen A-Dong, Master Beijing Children's Hospital of Capital Medical University
Study Director: Qi Yu-Jie, Master Beijing Children's Hospital of Capital Medical University
Study Director: Zhao Wei, Doctor Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital

Additional Information:

Publications of Results:
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Responsible Party: Adong Shen, Deputy Chief of China National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital
ClinicalTrials.gov Identifier: NCT03643497     History of Changes
Other Study ID Numbers: BCH_PPK004
First Posted: August 22, 2018    Key Record Dates
Last Update Posted: August 23, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Communicable Diseases
Infection
Linezolid
Meropenem
Anti-Infective Agents
Anti-Bacterial Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action