Children；InfectionNCT03643497
Population Pharmacokinetics of Meropenem and Linezolid in Children With Severe 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 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… 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?
- anti-infective drugs
- How many people
- 800 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2018to 31 Dec 2021
- 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: Severe infectious children with anti-infectious therapies
Who may be able to join
- 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
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 meropenem or linezolid.
- 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
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.
Read the detailed description
1.Establish population pharmacokinetic (PPK) models of meropenem and linezolid in severe infectious children by nonlinear mixed effect modeling (NONMEM).
- 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.
- Plasma and cerebrospinal fluid samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of meropenem and linezolid 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).
- Evaluation of the clinical feasibility and safety of individualized dosing.
- 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.
- 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
- Children；Infection
- Being tested
- anti-infective drugs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-infective drugsDrug
Also called meropenem, linezolid
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 | Children received meropenem or linezolid monotherapy in the treatment of seven infectious diseases Receives: Drug: anti-infective 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 posted22 Aug 2018
- Study start1 Jul 2018
- Primary completion30 Sep 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Shen A-Dong, Master, Principal investigator, Beijing Children's Hospital of Capital Medical UniversityQi Yu-Jie, Master, Study director, Beijing Children's Hospital of Capital Medical UniversityZhao Wei, Doctor, Study director, Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03643497
- Sponsor's protocol ID
- BCH_PPK004
- Status last verified
- Aug 2018
- First submitted
- 21 Aug 2018
- Last updated
- 23 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
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 25155587Wang 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.
PubMed 36278190Wang 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.
PubMed 32513801
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics of Meropenem and Linezolid in Children With Severe Infectious Diseases
- ClinicalTrials.gov ID
- NCT03643497
- Acronym / sponsor ID
- BCH_PPK004
- 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
- 1 Jul 2018 (actual)
- Primary completion
- 30 Sep 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 22 Aug 2018 (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 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
1.Establish population pharmacokinetic (PPK) models of meropenem and linezolid in severe infectious children by nonlinear mixed effect modeling (NONMEM).
- 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.
- Plasma and cerebrospinal fluid samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of meropenem and linezolid 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).
- Evaluation of the clinical feasibility and safety of individualized dosing.
- 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.
- 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 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: anti-infective drugsChildren received meropenem or linezolid monotherapy in the treatment of seven infectious diseases |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Severe infectious children with anti-infectious therapies
Key inclusion criteria (4 listed)
- 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
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 meropenem or linezolid.
- 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 |
|---|---|---|
| anti-infective drugsAlso: meropenem, linezolidAccording 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 23 Aug 2018.
- 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 36278190Wang 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.
- Derived from this study: PubMed 32513801Wang 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.
- Individual participant dataSharing planned: Yes
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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.
Shen A-Dong, Master principal investigator
Beijing Children's Hospital of Capital Medical University
Qi Yu-Jie, Master study director
Beijing Children's Hospital of Capital Medical University
Zhao Wei, 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 23 Aug 2018. 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 Shen A-Dong, Master (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 NCT03643497, which also lists 5 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 23 Aug 2018.