Critical IllnessPOPSICLENCT03248349
Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)
An observational study of Critical Illness and Infectious Disease, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Infections are common on the Intensive Care for both adult and pediatric patients. Adequately dosing antibiotic treatment is of vital importance but both under- and overdosing is frequent due to pathophysiological changes during critical illness. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Critical Illness, Infectious Disease, Children
- What is being tested?
- Pharmacokinetics
- How many people
- 200 participants
- Where
- 1 siteNetherlands
- Study dates
- 24 May 2017to 1 Oct 2020
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Critically ill children receiving antibiotics.
Who may be able to join
- 0 to 18 years of postnatal age;
- >37 weeks of gestational age (in children less than 6 months of postnatal age);
- Admitted to pediatric intensive care unit;
- Indwelling central line or arterial line in place for clinical purposes, or regular blood work for clinical reasons;
- Antibiotic therapy already prescribed by treating physician;
- Written informed consent (IC).
Who cannot join
- Language or cognitive inability to understand written and oral informed consent.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Radboudumc
Nijmegen, Gelderland, 6525GA
Stan JF Hartman, M.D., +31622739795, Stan.Hartman@radboudumc.nl
Saskia N de Wildt, prof. M.D.
About this study
Official title: Population Pharmacokinetics of Antibiotics in Critically Ill Children
Infections are common on the Intensive Care for both adult and pediatric patients. Adequately dosing antibiotic treatment is of vital importance but both under- and overdosing is frequent due to pathophysiological changes during critical illness. Moreover, the interplay of age and critical illness is even more understudied.
To optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed. In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.
Read the detailed description
Approximately one third of all critically ill children develop infectious disease related complications. Mortality due to infections can be as high as 30-45%. In up to 41% of adult critically ill patients antimicrobial dosing recommendations are inadequate, as acute kidney injury, augmented renal clearance, inflammatory response and hypoalbuminaemia all contribute to variation in drug concentrations. This is an important reason for antibiotic treatment failure and emergence of resistance.
Data from adults cannot be directly extrapolated to children, due to developmental changes in the processes involved in drug disposition. Moreover, the interplay of age and critical illness is even more understudied. Hence, to optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed.
In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.
Objectives:
To determine the population pharmacokinetics of antibiotics in critically ill pediatric patients to develop individualized dosing guidelines for antibiotics for this population.
Study design:
Observational study with minimal invasive procedures: population pharmacokinetic study.
Study population:
Critically ill children, admitted on the pediatric intensive care unit (PICU), receiving antibiotics.
Study parameters/endpoints:
Primary:
- To estimate population pharmacokinetic parameters for antibiotics
Secondary:
- To determine the target attainment rate of antibiotic exposure
- To design individualized dosing guidelines for antibiotics
Exploratory:
- To describe variability in kidney function
- To explore the relationship of genetic variation with disposition of pharmacokinetics.
- Conditions
- Critical Illness, Infectious Disease, Children
- Being tested
- Pharmacokinetics
- Keywords
- Critically ill children, Pharmacokinetics, Anti-Bacterial agents
- Medical subject headings
- Critical Illness, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PharmacokineticsDrug
Also called Antibiotics
- Blood samples are drawn for pharmacokinetic properties of antibiotics during routine care treatment
- Blood samples for relevant covariates of drug disposition (kidney function, liver enzymes, C-reactive protein (CRP), albumin)
- Whole blood is stored for DNA analysis
- Urine is drawn from catheter for more detailed estimation of glomerular filtration rate and drug metabolite analysis
| Study group | Role | What they receive |
|---|---|---|
| 1 | Pharmacokinetics Receives: Drug: Pharmacokinetics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume of distribution of antibiotics in critically ill children
Population mean value of volume of distribution of antibiotics during critical illness. Mean population volume of distribution will be derived from pooled data of antibiotic concentrations. Covariates of influence on volume of distribution will be incorporated within a population pharmacokinetic model.
Measured: 14 days
Clearance of antibiotics in critically ill children
Population mean value of clearance of antibiotics during critical illness. Mean population clearance will be derived from pooled data of antibiotic concentrations. Covariates of influence on drug clearance will be incorporated within a population pharmacokinetic model.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2017
- Study start24 May 2017
- Primary completion1 May 2020 (estimated)
- Study completion1 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Saskia N de Wildt, Prof. M.D., Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03248349
- Sponsor's protocol ID
- 2016-3085
- Acronym
- POPSICLE
- Status last verified
- Sep 2019
- First submitted
- 2 Aug 2017
- Last updated
- 13 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hartman SJF, Upadhyay PJ, Mathot RAA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Population pharmacokinetics of intravenous cefotaxime indicates that higher doses are required for critically ill children. J Antimicrob Chemother. 2022 May 29;77(6):1725-1732. doi: 10.1093/jac/dkac095.
PubMed 35383374Hartman SJF, Upadhyay PJ, Hagedoorn NN, Mathot RAA, Moll HA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Current Ceftriaxone Dose Recommendations are Adequate for Most Critically Ill Children: Results of a Population Pharmacokinetic Modeling and Simulation Study. Clin Pharmacokinet. 2021 Oct;60(10):1361-1372. doi: 10.1007/s40262-021-01035-9. Epub 2021 May 26.
PubMed 34036552
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics of Antibiotics in Critically Ill Children
- ClinicalTrials.gov ID
- NCT03248349
- Acronym / sponsor ID
- POPSICLE / 2016-3085
- Conditions
- Critical Illness, Infectious Disease, Children
- Keywords
- Critically ill children, Pharmacokinetics, Anti-Bacterial agents
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 24 May 2017 (actual)
- Primary completion
- 1 May 2020 (estimated)
- Study completion
- 1 Oct 2020 (estimated)
- First posted
- 14 Aug 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.
Infections are common on the Intensive Care for both adult and pediatric patients. Adequately dosing antibiotic treatment is of vital importance but both under- and overdosing is frequent due to pathophysiological changes during critical illness. Moreover, the interplay of age and critical illness is even more understudied.
To optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed. In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.
Detailed description
Approximately one third of all critically ill children develop infectious disease related complications. Mortality due to infections can be as high as 30-45%. In up to 41% of adult critically ill patients antimicrobial dosing recommendations are inadequate, as acute kidney injury, augmented renal clearance, inflammatory response and hypoalbuminaemia all contribute to variation in drug concentrations. This is an important reason for antibiotic treatment failure and emergence of resistance.
Data from adults cannot be directly extrapolated to children, due to developmental changes in the processes involved in drug disposition. Moreover, the interplay of age and critical illness is even more understudied. Hence, to optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed.
In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.
Objectives:
To determine the population pharmacokinetics of antibiotics in critically ill pediatric patients to develop individualized dosing guidelines for antibiotics for this population.
Study design:
Observational study with minimal invasive procedures: population pharmacokinetic study.
Study population:
Critically ill children, admitted on the pediatric intensive care unit (PICU), receiving antibiotics.
Study parameters/endpoints:
Primary:
- To estimate population pharmacokinetic parameters for antibiotics
Secondary:
- To determine the target attainment rate of antibiotic exposure
- To design individualized dosing guidelines for antibiotics
Exploratory:
- To describe variability in kidney function
- To explore the relationship of genetic variation with disposition of pharmacokinetics.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: PharmacokineticsPharmacokinetics |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Critically ill children receiving antibiotics.
Key inclusion criteria (6 listed)
- 0 to 18 years of postnatal age;
- >37 weeks of gestational age (in children less than 6 months of postnatal age);
- Admitted to pediatric intensive care unit;
- Indwelling central line or arterial line in place for clinical purposes, or regular blood work for clinical reasons;
- Antibiotic therapy already prescribed by treating physician;
Key exclusion criteria (1 listed)
- Language or cognitive inability to understand written and oral informed consent.
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 |
|---|---|---|
| PharmacokineticsAlso: Antibiotics* Blood samples are drawn for pharmacokinetic properties of antibiotics during routine care treatment * Blood samples for relevant covariates of drug disposition (kidney function, liver enzymes, C-reactive protein (CRP), albumin) * Whole blood is stored for DNA analysis * Urine is drawn from catheter for more detailed estimation of glomerular filtration rate and drug metabolite analysis | Drug | 1 |
Primary outcome
Volume of distribution of antibiotics in critically ill children
Time frame: 14 days
Population mean value of volume of distribution of antibiotics during critical illness. Mean population volume of distribution will be derived from pooled data of antibiotic concentrations. Covariates of influence on volume of distribution will be incorporated within a population pharmacokinetic model.
Clearance of antibiotics in critically ill children
Time frame: 14 days
Population mean value of clearance of antibiotics during critical illness. Mean population clearance will be derived from pooled data of antibiotic concentrations. Covariates of influence on drug clearance will be incorporated within a population pharmacokinetic model.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2020.
- Derived from this study: PubMed 35383374Hartman SJF, Upadhyay PJ, Mathot RAA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Population pharmacokinetics of intravenous cefotaxime indicates that higher doses are required for critically ill children. J Antimicrob Chemother. 2022 May 29;77(6):1725-1732. doi: 10.1093/jac/dkac095.
- Derived from this study: PubMed 34036552Hartman SJF, Upadhyay PJ, Hagedoorn NN, Mathot RAA, Moll HA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Current Ceftriaxone Dose Recommendations are Adequate for Most Critically Ill Children: Results of a Population Pharmacokinetic Modeling and Simulation Study. Clin Pharmacokinet. 2021 Oct;60(10):1361-1372. doi: 10.1007/s40262-021-01035-9. Epub 2021 May 26.
- Individual participant dataSharing planned: No
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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.
Saskia N de Wildt, Prof. M.D. principal investigator
Radboud University Medical Center
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 Critical Illness and Infectious Disease, run by Radboud University Medical Center at 1 site in Netherlands.
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 6 inclusion and 1 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 13 Mar 2020. 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 Netherlands. 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 Stan JF Hartman, M.D. (+31622739795, Stan.Hartman@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume of distribution of antibiotics in critically ill children (time frame: 14 days). The study lists 2 primary outcomes in all. 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 NCT03248349, which also lists 2 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 13 Mar 2020.