<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03248349</url>
  </required_header>
  <id_info>
    <org_study_id>2016-3085</org_study_id>
    <nct_id>NCT03248349</nct_id>
  </id_info>
  <brief_title>Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)</brief_title>
  <acronym>POPSICLE</acronym>
  <official_title>Population Pharmacokinetics of Antibiotics in Critically Ill Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Infections are common on the Intensive Care for both adult and pediatric patients. Adequately&#xD;
      dosing antibiotic treatment is of vital importance but both under- and overdosing is frequent&#xD;
      due to pathophysiological changes during critical illness. Moreover, the interplay of age and&#xD;
      critical illness is even more understudied.&#xD;
&#xD;
      To optimize antibiotic dosing and outcome of infectious disease, personalized dosing&#xD;
      guidelines in critically ill patients are highly needed. In this prospective observational&#xD;
      population pharmacokinetic study we will evaluate if target attainment for antibiotics is&#xD;
      reached in critically ill children with current dosing guidelines. Using these data,&#xD;
      individualized dosing guidelines will be developed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately one third of all critically ill children develop infectious disease related&#xD;
      complications. Mortality due to infections can be as high as 30-45%. In up to 41% of adult&#xD;
      critically ill patients antimicrobial dosing recommendations are inadequate, as acute kidney&#xD;
      injury, augmented renal clearance, inflammatory response and hypoalbuminaemia all contribute&#xD;
      to variation in drug concentrations. This is an important reason for antibiotic treatment&#xD;
      failure and emergence of resistance.&#xD;
&#xD;
      Data from adults cannot be directly extrapolated to children, due to developmental changes in&#xD;
      the processes involved in drug disposition. Moreover, the interplay of age and critical&#xD;
      illness is even more understudied. Hence, to optimize antibiotic dosing and outcome of&#xD;
      infectious disease, personalized dosing guidelines in critically ill patients are highly&#xD;
      needed.&#xD;
&#xD;
      In this prospective observational population pharmacokinetic study we will evaluate if target&#xD;
      attainment for antibiotics is reached in critically ill children with current dosing&#xD;
      guidelines. Using these data, individualized dosing guidelines will be developed.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To determine the population pharmacokinetics of antibiotics in critically ill pediatric&#xD;
      patients to develop individualized dosing guidelines for antibiotics for this population.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      Observational study with minimal invasive procedures: population pharmacokinetic study.&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      Critically ill children, admitted on the pediatric intensive care unit (PICU), receiving&#xD;
      antibiotics.&#xD;
&#xD;
      Study parameters/endpoints:&#xD;
&#xD;
      Primary:&#xD;
&#xD;
        -  To estimate population pharmacokinetic parameters for antibiotics&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  To determine the target attainment rate of antibiotic exposure&#xD;
&#xD;
        -  To design individualized dosing guidelines for antibiotics&#xD;
&#xD;
      Exploratory:&#xD;
&#xD;
        -  To describe variability in kidney function&#xD;
&#xD;
        -  To explore the relationship of genetic variation with disposition of pharmacokinetics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 24, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Volume of distribution of antibiotics in critically ill children</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clearance of antibiotics in critically ill children</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Critical Illness</condition>
  <condition>Infectious Disease</condition>
  <condition>Children</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <description>Pharmacokinetics</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pharmacokinetics</intervention_name>
    <description>Blood samples are drawn for pharmacokinetic properties of antibiotics during routine care treatment&#xD;
Blood samples for relevant covariates of drug disposition (kidney function, liver enzymes, C-reactive protein (CRP), albumin)&#xD;
Whole blood is stored for DNA analysis&#xD;
Urine is drawn from catheter for more detailed estimation of glomerular filtration rate and drug metabolite analysis</description>
    <arm_group_label>1</arm_group_label>
    <other_name>Antibiotics</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  Blood plasma for antibiotic concentrations during admission (max. 14 days)&#xD;
&#xD;
        -  Whole blood sample for future DNA-analysis&#xD;
&#xD;
        -  Urine samples during admission (max. 14 days)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Critically ill children receiving antibiotics.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  0 to 18 years of postnatal age;&#xD;
&#xD;
          -  &gt;37 weeks of gestational age (in children less than 6 months of postnatal age);&#xD;
&#xD;
          -  Admitted to pediatric intensive care unit;&#xD;
&#xD;
          -  Indwelling central line or arterial line in place for clinical purposes, or regular&#xD;
             blood work for clinical reasons;&#xD;
&#xD;
          -  Antibiotic therapy already prescribed by treating physician;&#xD;
&#xD;
          -  Written informed consent (IC).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Language or cognitive inability to understand written and oral informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Saskia N de Wildt, Prof. M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Stan JF Hartman, M.D.</last_name>
    <phone>+31622739795</phone>
    <email>Stan.Hartman@radboudumc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6525GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stan JF Hartman, M.D.</last_name>
      <phone>+31622739795</phone>
      <email>Stan.Hartman@radboudumc.nl</email>
    </contact>
    <investigator>
      <last_name>Saskia N de Wildt, prof. M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stan JF Hartman, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>March 12, 2020</last_update_submitted>
  <last_update_submitted_qc>March 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Critically ill children</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Anti-Bacterial agents</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Infections</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 2, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03248349
org study id: 2016-3085
nct id: NCT03248349
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
observational model: Cohort
time perspective: Prospective
measure: Volume of distribution of antibiotics in critically ill children
time frame: 14 days
description: 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.
measure: Clearance of antibiotics in critically ill children
time frame: 14 days
description: 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.
arm group label: 1
description: Pharmacokinetics
intervention type: Drug
intervention name: Pharmacokinetics
description: 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
arm group label: 1
other name: Antibiotics
-  Blood plasma for antibiotic concentrations during admission (max. 14 days)

        -  Whole blood sample for future DNA-analysis

        -  Urine samples during admission (max. 14 days)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Saskia N de Wildt, Prof. M.D.
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Stan JF Hartman, M.D.
phone: +31622739795
email: Stan.Hartman@radboudumc.nl
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Netherlands
responsible party type: Sponsor
mesh term: Communicable Diseases
mesh term: Infections
mesh term: Critical Illness
mesh term: Anti-Bacterial Agents
sharing ipd: No
submitted: May 2, 2023