Children; InfectionNCT03113344
Population Pharmacokinetics of Anti-infective Drugs in Children With Infectious Diseases
An observational study of Children; Infection, run by Beijing Children's Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Children; Infection
- What is being tested?
- cephalosporins,penicillins,macrolides,carbapenems and antiviral drugs
- How many people
- 800 participants
- Where
- 1 siteChina
- Study dates
- 21 Jun 2017to 31 Dec 2025
- How long will I take part?
- 18 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children with anti-infectious therapies.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Children's Hospital of Capital Medical University
Beijing
Adong Shen, Master, 13370115087, shenad16@hotmail.com
About this study
Official title: Population Pharmacokinetics of Anti-infective Drugs in Children in Anti-infectious Therapies
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.
Read the detailed description
1.Establish population pharmacokinetic (PPK) models of each anti-infective drug in children by nonlinear mixed effect modeling (NONMEM).
- 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 .
- Plasma samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of antibiotics will be established by NONMEM program.
- 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.
- 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.
- 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
- Children; Infection
- Being tested
- cephalosporins,penicillins,macrolides,carbapenems and antiviral drugs
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cephalosporins,penicillins,macrolides,carbapenems and antiviral drugsDrug
Also called latamoxef, ceftriaxone, ceftazidime, ampicillin
According to the models of population pharmacokinetics,the investigators and want to correlate use of antibiotics with treatment effectiveness and safety in children.
| Study group | Role | What they receive |
|---|---|---|
| Children with the usage of anti-infective drugs | Not described Receives: Drug: cephalosporins,penicillins,macrolides,carbapenems and antiviral drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 4 weeks
Secondary outcomes (4)
time to achieve maximum concentration (Tmax)
Tmax is the term used in pharmacokinetics to describe the time at which the Cmax is observed.
Measured: up to 4 weeks
absorption rate constant (ka)
Ka is the rate constant of drug absorption.
Measured: up to 4 weeks
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.
Measured: up to 4 weeks
half-life (t1/2)
Half-life is the time required for a quantity to reduce to half its initial value.
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start21 Jun 2017
- Primary completion1 Oct 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Children; InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 800 participants (estimated)
- Target duration
- 18 Years
Sponsor and investigators
- Lead sponsor
- Beijing Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong University, Hopital Universitaire Robert-Debre, Rennes University Hospital
- Responsible party
- Principal investigator, Adong Shen, Beijing Children's Hospital
- Investigators
- A-Dong Shen, Master, Principal investigator, Beijing Children's Hospital of Capital Medical UniversityYu-Jie Qi, Master, Study director, Beijing Children's Hospital of Capital Medical UniversityWei Zhao, Doctor, Study director, Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03113344
- Sponsor's protocol ID
- BCH_PPK002
- Other IDs
- Yu-Jie Qi, Wei Zhao, Hui Qi, Fei Jin, Evelyne Jacqz-Aigrain, Stephanie Leroux
- Status last verified
- Dec 2017
- First submitted
- 10 Apr 2017
- Last updated
- 19 Dec 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 23254142Leroux 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.
PubMed 25628457Jacqz-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.
PubMed 26289222Ramos-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.
PubMed 26755499Zhao 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.
PubMed 25155587Kan 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.
PubMed 33020163Shi 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.
PubMed 32129861Dong 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.
PubMed 30962334Dong 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.
PubMed 29507070
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics of Anti-infective Drugs in Children in Anti-infectious Therapies
- ClinicalTrials.gov ID
- NCT03113344
- Acronym / sponsor ID
- BCH_PPK002
- Conditions
- Children; Infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Beijing Children's HospitalUniversity, hospital or other
- Collaborators
- Shandong University, Hopital Universitaire Robert-Debre, Rennes University Hospital
- Study start
- 21 Jun 2017 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 13 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
1.Establish population pharmacokinetic (PPK) models of each anti-infective drug in children by nonlinear mixed effect modeling (NONMEM).
- 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 .
- Plasma samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of antibiotics will be established by NONMEM program.
- 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.
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 18 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with the usage of anti-infective drugs | – | Drug: cephalosporins,penicillins,macrolides,carbapenems and antiviral drugs |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children with anti-infectious therapies.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cephalosporins,penicillins,macrolides,carbapenems and antiviral drugsAlso: latamoxef, ceftriaxone, ceftazidime, ampicillinAccording to the models of population pharmacokinetics,the investigators and want to correlate use of antibiotics with treatment effectiveness and safety in children. | Drug | Children with the usage of anti-infective drugs |
Primary outcome
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.
4 secondary outcomes
time to achieve maximum concentration (Tmax)
Time frame: up to 4 weeks
absorption rate constant (ka)
Time frame: up to 4 weeks
elimination rate constant (kel)
Time frame: up to 4 weeks
half-life (t1/2)
Time frame: up to 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2017.
- Results publication: PubMed 23254142Zhao 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.
- Results publication: PubMed 25628457Leroux 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.
- Results publication: PubMed 26289222Jacqz-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.
- Results publication: PubMed 26755499Ramos-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.
- Results publication: PubMed 25155587Zhao 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.
- Derived from this study: PubMed 33020163Kan 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.
- Derived from this study: PubMed 32129861Shi 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.
- Derived from this study: PubMed 30962334Dong 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.
- Derived from this study: PubMed 29507070Dong 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A-Dong Shen, Master principal investigator
Beijing Children's Hospital of Capital Medical University
Yu-Jie Qi, Master study director
Beijing Children's Hospital of Capital Medical University
Wei Zhao, Doctor study director
Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Children; Infection, run by Beijing Children's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact A-Dong Shen, Master (+86-010-59616898, shenad16@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
maximum concentration (Cmax) (time frame: up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03113344, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2017.