Population Pharmacokinetics of Anti-infective Drugs in Children With Infectious Diseases

NCT ID: NCT03113344

Last Updated: 2017-12-19

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

RECRUITING

Total Enrollment

800 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-06-21

Study Completion Date

2025-12-31

Brief Summary

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This study is based on the hypothesis that the pharmacokinetics of anti-infective drugs in children are different from adults. We aim to study the population pharmacokinetics of children receiving the anti-infective drugs for treatment of infectious diseases. In this study, we 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, we also want to correlate use of anti-infective 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 infectious diseases in children. It will also set the foundation for further studies to improve anti-infective drug therapies for children.

Detailed Description

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1.Establish population pharmacokinetic (PPK) models of each anti-infective drug in children by nonlinear mixed effect modeling (NONMEM).

1. At different timepoint after antibiotic 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 antibiotics 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, we will use dosages recommended in models to cure children infectious diseases in prospective studies. For each antibiotic, 50 children will be collected.
2. We 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.

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

cephalosporins,penicillins,macrolides,carbapenems and antiviral 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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cephalosporins,penicillins,macrolides,carbapenems and antiviral 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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latamoxef ceftriaxone ceftazidime ampicillin penicillin amoxicillin erythromycin azithromycin meropenem imipenem ganciclovir acyclovir

Eligibility Criteria

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Inclusion Criteria

* Children (0-18 years old) with anti-infective therapy against infectious diseases.
* The anti-infective therapy includes drugs commonly used in children infectious diseases, for example, cephalosporins (such as latamoxef, ceftazidime, ceftriaxone and so on), penicillins (such as penicillin, amoxicillin, ampicillin and so on), macrolides (such as erythromycin, azithromycin and so on), carbapenems (sucn as meropenem, imipenem and so on) and antiviral drugs (such as ganciclovir, acyclovir and so on).
* Children infectious diseases include pneumonia, sepsis, purulent meningitis and other diseases with 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 anti-infective drugs.
* 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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A-Dong Shen, Master

Role: PRINCIPAL_INVESTIGATOR

Beijing Children's Hospital of Capital Medical University

Yu-Jie Qi, Master

Role: STUDY_DIRECTOR

Beijing Children's Hospital of Capital Medical University

Wei Zhao, 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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A-Dong Shen, Master

Role: CONTACT

Phone: +86-010-59616898

Email: [email protected]

Facility Contacts

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Adong Shen, Master

Role: primary

References

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Zhao W, Lopez E, Biran V, Durrmeyer X, Fakhoury M, Jacqz-Aigrain E. Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring. Arch Dis Child. 2013 Jun;98(6):449-53. doi: 10.1136/archdischild-2012-302765. Epub 2012 Dec 19.

Reference Type RESULT
PMID: 23254142 (View on PubMed)

Leroux S, Zhao W, Betremieux P, Pladys P, Saliba E, Jacqz-Aigrain E; French Society of Neonatology. Therapeutic guidelines for prescribing antibiotics in neonates should be evidence-based: a French national survey. Arch Dis Child. 2015 Apr;100(4):394-8. doi: 10.1136/archdischild-2014-306873. Epub 2015 Jan 27.

Reference Type RESULT
PMID: 25628457 (View on PubMed)

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)

Kan M, Shi HY, Han B, Wu YE, Li Q, Guo ZX, Li X, Hao GX, Zheng Y, Su LQ, Huang X, Sui ZG, Zhao W. Prediction of Unbound Ceftriaxone Concentration in Children: Simple Bioanalysis Method and Basic Mathematical Equation. Antimicrob Agents Chemother. 2020 Dec 16;65(1):e00779-20. doi: 10.1128/AAC.00779-20. Print 2020 Dec 16.

Reference Type DERIVED
PMID: 33020163 (View on PubMed)

Shi HY, Wang K, Wang RH, Wu YE, Tang BH, Li X, Du B, Kan M, Zheng Y, Xu BP, Shen AD, Su LQ, Jacqz-Aigrain E, Huang X, Zhao W. Developmental population pharmacokinetics-pharmacodynamics and dosing optimization of cefoperazone in children. J Antimicrob Chemother. 2020 Jul 1;75(7):1917-1924. doi: 10.1093/jac/dkaa071.

Reference Type DERIVED
PMID: 32129861 (View on PubMed)

Dong L, Zhai XY, Yang YL, Wang L, Zhou Y, Shi HY, Tang BH, Wu YE, Yang F, Wen L, Kong HX, Zhi LJ, Jacqz-Aigrain E, Zhao W. Population Pharmacokinetics and Dosing Optimization of Imipenem in Children with Hematological Malignancies. Antimicrob Agents Chemother. 2019 May 24;63(6):e00006-19. doi: 10.1128/AAC.00006-19. Print 2019 Jun.

Reference Type DERIVED
PMID: 30962334 (View on PubMed)

Dong Q, Leroux S, Shi HY, Xu HY, Kou C, Khan MW, Jacqz-Aigrain E, Zhao W. Pilot Study of Model-Based Dosage Individualization of Ganciclovir in Neonates and Young Infants with Congenital Cytomegalovirus Infection. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e00075-18. doi: 10.1128/AAC.00075-18. Print 2018 May.

Reference Type DERIVED
PMID: 29507070 (View on PubMed)

Other Identifiers

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Yu-Jie Qi

Identifier Type: OTHER

Identifier Source: secondary_id

Wei Zhao

Identifier Type: OTHER

Identifier Source: secondary_id

Hui Qi

Identifier Type: OTHER

Identifier Source: secondary_id

Fei Jin

Identifier Type: OTHER

Identifier Source: secondary_id

Evelyne Jacqz-Aigrain

Identifier Type: OTHER

Identifier Source: secondary_id

Stephanie Leroux

Identifier Type: OTHER

Identifier Source: secondary_id

BCH_PPK002

Identifier Type: -

Identifier Source: org_study_id