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

NCT ID: NCT03643497

Last Updated: 2018-08-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

800 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-07-01

Study Completion Date

2021-12-31

Brief Summary

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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.

Detailed Description

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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

Conditions

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Children;Infection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Children with the usage of anti-infective drugs

Children received meropenem or linezolid monotherapy in the treatment of seven infectious diseases

anti-infective drugs

Intervention Type DRUG

According to the models of population pharmacokinetics, the investigators and want to correlate use of antibiotics with treatment effectiveness and safety in children

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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meropenem linezolid

Eligibility Criteria

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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.
Minimum Eligible Age

1 Day

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shandong University

OTHER

Sponsor Role collaborator

Hopital Universitaire Robert-Debre

OTHER

Sponsor Role collaborator

Rennes University Hospital

OTHER

Sponsor Role collaborator

Beijing Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Adong Shen

Deputy Chief of China National Clinical Research Center for Respiratory Diseases

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shen A-Dong, Master

Role: PRINCIPAL_INVESTIGATOR

Beijing Children's Hospital of Capital Medical University

Qi Yu-Jie, Master

Role: STUDY_DIRECTOR

Beijing Children's Hospital of Capital Medical University

Zhao Wei, Doctor

Role: STUDY_DIRECTOR

Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital

Locations

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Beijing Children's Hospital of Capital Medical University

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Shen A-Dong, Master

Role: CONTACT

010-59616898

Facility Contacts

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Adong Shen, Master

Role: primary

13370115087

References

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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.

Reference Type RESULT
PMID: 26289222 (View on PubMed)

Ramos-Martin V, Johnson A, Livermore J, McEntee L, Goodwin J, Whalley S, Docobo-Perez 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 vancomycin in neonates. J Antimicrob Chemother. 2016 Apr;71(4):992-1002. doi: 10.1093/jac/dkv451. Epub 2016 Jan 10.

Reference Type RESULT
PMID: 26755499 (View on PubMed)

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 of age. Antimicrob Agents Chemother. 2014 Nov;58(11):6572-80. doi: 10.1128/AAC.03568-14. Epub 2014 Aug 25.

Reference Type RESULT
PMID: 25155587 (View on PubMed)

Wang Z, Bi J, You D, Tang Y, Liu G, Yu J, Jin Z, Jiang T, Tian X, Qi H, Dong L, Dong L, Zhang Q, Zhao W, Shen A. Improving the efficacy for meropenem therapy requires a high probability of target attainment in critically ill infants and children. Front Pharmacol. 2022 Oct 5;13:961863. doi: 10.3389/fphar.2022.961863. eCollection 2022.

Reference Type DERIVED
PMID: 36278190 (View on PubMed)

Wang ZM, Chen XY, Bi J, Wang MY, Xu BP, Tang BH, Li C, Zhao W, Shen AD. Reappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic Analysis. Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00760-20. doi: 10.1128/AAC.00760-20. Print 2020 Jul 22.

Reference Type DERIVED
PMID: 32513801 (View on PubMed)

Other Identifiers

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BCH_PPK004

Identifier Type: -

Identifier Source: org_study_id

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