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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03643497
Other study ID # BCH_PPK004
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date July 1, 2018
Est. completion date December 31, 2021

Study information

Verified date August 2018
Source Beijing Children's Hospital
Contact Shen A-Dong, Master
Phone 010-59616898
Email shenad16@hotmail.com
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial 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.


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


Recruitment information / eligibility

Status Recruiting
Enrollment 800
Est. completion date December 31, 2021
Est. primary completion date September 30, 2021
Accepts healthy volunteers No
Gender All
Age group N/A to 18 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
China Beijing Children's Hospital of Capital Medical University Beijing

Sponsors (4)

Lead Sponsor Collaborator
Beijing Children's Hospital Centre Hospitalier Universitaire de Rennes, Robert Debré Hospital, Shandong University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. Review. — View Citation

Ramos-Martín V, Johnson A, Livermore J, McEntee L, Goodwin J, Whalley S, Docobo-Pérez F, Felton TW, Zhao W, Jacqz-Aigrain E, Sharland M, Turner MA, Hope WW. Pharmacodynamics of vancomycin for CoNS infection: experimental basis for optimal use of vancomyci — View Citation

Zhao W, Hill H, Le Guellec C, Neal T, Mahoney S, Paulus S, Castellan C, Kassai B, van den Anker JN, Kearns GL, Turner MA, Jacqz-Aigrain E; TINN Consortium. Population pharmacokinetics of ciprofloxacin in neonates and young infants less than three months o — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary maximum concentration (Cmax) 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 time to achieve maximum concentration (Tmax) Tmax is the term used in pharmacokinetics to describe the time at which the Cmax is observed up to 4 weeks
Secondary absorption rate constant (ka) Ka is the rate constant of drug absorption up to 4 weeks
Secondary elimination rate constant (kel) 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
Secondary half-life (t1/2) Half-life is the time required for a quantity to reduce to half its initial value up to 4 weeks