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

August 22, 2018 updated by: Adong Shen, Beijing Children's Hospital
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Study Type

Observational

Enrollment (Anticipated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Beijing Children's Hospital of Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Severe infectious children with anti-infectious therapies

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 4 weeks
absorption rate constant (ka)
Time Frame: up to 4 weeks
Ka is the rate constant of drug absorption
up to 4 weeks
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
up to 4 weeks
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
up to 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Children's Hospital

Collaborators

Hopital Universitaire Robert-Debre
Shandong University
Rennes University Hospital

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Anticipated)

September 30, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

August 21, 2018

First Submitted That Met QC Criteria

August 21, 2018

First Posted (Actual)

August 22, 2018

Study Record Updates

Last Update Posted (Actual)

August 23, 2018

Last Update Submitted That Met QC Criteria

August 22, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCH_PPK004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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