<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/NCT04470973</url>
  </required_header>
  <id_info>
    <org_study_id>PHARAOH</org_study_id>
    <nct_id>NCT04470973</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Amikacin and Cefuroxime in Critically Ill Patients.</brief_title>
  <acronym>PHARAOH</acronym>
  <official_title>Population Pharmacokinetics of Amikacin and Cefuroxime in Critically Ill Septic Patients Admitted to the ICU or the ED</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 in critically ill patients are a major healthcare problem and an important source&#xD;
      of morbidity and mortality. Since critically ill patients often have altered pharmacokinetics&#xD;
      (PK) compared to non-critically ill patients there is a substantial risk that present&#xD;
      standard dosing regimens of antibiotics lead to suboptimal outcomes for patients on the ICU&#xD;
      or the ED. To prevent the risk of inadequate dosing in ICU patients, it is important to fully&#xD;
      understand the PK of antibiotics in this vulnerable group in order to optimize the dosing&#xD;
      regimens.&#xD;
&#xD;
      With this study, the investigators will describe the pharmacokinetics of cefuroxime and&#xD;
      amikacin in ICU and ED patients. A heterogeneous population of ICU and ED patients will be&#xD;
      included to be able to find which factors might influence the pharmacokinetics of these drugs&#xD;
      and to what extent. By using population modeling the investigators will simulate different&#xD;
      dosing regimens and MIC values and compare probability of target attainment between each of&#xD;
      these dose and MIC combinations. This will allow the investigators to optimize dosing&#xD;
      regimens of cefuroxime and amikacin in critically ill patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2023</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>To describe the population pharmacokinetics of amikacin in Intensive Care or Emergency Department patients</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To describe the population pharmacokinetics of cefuroxime in Intensive Care or Emergency Department patients</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine the influence of renal clearance and weight on the pharmacokinetics of amikacin and cefuroxime</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the proportion of patients who attain adequate PK/PD targets in relation to the MIC of the suspected pathogen.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the toxicity of amikacin</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>To investigate to what extend renal replacement therapy affects the pharmacokinetics of amikacin and cefuroxime</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Sepsis</condition>
  <condition>Septic Shock</condition>
  <condition>Infection, Bacterial</condition>
  <condition>Critically Ill</condition>
  <arm_group>
    <arm_group_label>Cefuroxime/Amikacin</arm_group_label>
    <description>20 patients will be included in the cefuroxime cohort and 20 patients in the amikacin cohort.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cefuroxime</intervention_name>
    <description>Patients receive cefuroxime as part of standard care.</description>
    <arm_group_label>Cefuroxime/Amikacin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amikacin</intervention_name>
    <description>Patients receive amikacin as part of standard care.</description>
    <arm_group_label>Cefuroxime/Amikacin</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples and 24 hours urine will be collection following an intravenous gift of either&#xD;
      cefuroxime or amikacin.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Critically ill patients admitted to the ICU or ED.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient is admitted to the ICU or ED;&#xD;
&#xD;
          2. The patient is at least 18 years of age on the day of inclusion;&#xD;
&#xD;
          3. Is managed with a central venous catheter or arterial line;&#xD;
&#xD;
          4. Is treated with amikacin and/or cefuroxime as standard care.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Has previously participated in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roger Brüggemann, Phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Julian Machiels, MD, MSc</last_name>
    <phone>+31243614369</phone>
    <email>julian.machiels@radboudumc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Radboudumc intensive care</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>J Machiels</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>September 9, 2022</last_update_submitted>
  <last_update_submitted_qc>September 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>Septic Shock</keyword>
  <keyword>Infection</keyword>
  <keyword>Critically Ill</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Bacterial 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>Amikacin</mesh_term>
    <mesh_term>Cefuroxime</mesh_term>
    <mesh_term>Cefuroxime axetil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04470973
org study id: PHARAOH
nct id: NCT04470973
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Infections in critically ill patients are a major healthcare problem and an important source
      of morbidity and mortality. Since critically ill patients often have altered pharmacokinetics
      (PK) compared to non-critically ill patients there is a substantial risk that present
      standard dosing regimens of antibiotics lead to suboptimal outcomes for patients on the ICU
      or the ED. To prevent the risk of inadequate dosing in ICU patients, it is important to fully
      understand the PK of antibiotics in this vulnerable group in order to optimize the dosing
      regimens.

      With this study, the investigators will describe the pharmacokinetics of cefuroxime and
      amikacin in ICU and ED patients. A heterogeneous population of ICU and ED patients will be
      included to be able to find which factors might influence the pharmacokinetics of these drugs
      and to what extent. By using population modeling the investigators will simulate different
      dosing regimens and MIC values and compare probability of target attainment between each of
      these dose and MIC combinations. This will allow the investigators to optimize dosing
      regimens of cefuroxime and amikacin in critically ill patients.
observational model: Cohort
time perspective: Prospective
measure: To describe the population pharmacokinetics of amikacin in Intensive Care or Emergency Department patients
time frame: 1 year
measure: To describe the population pharmacokinetics of cefuroxime in Intensive Care or Emergency Department patients
time frame: 1 year
measure: To determine the influence of renal clearance and weight on the pharmacokinetics of amikacin and cefuroxime
time frame: 1 year
measure: To determine the proportion of patients who attain adequate PK/PD targets in relation to the MIC of the suspected pathogen.
time frame: 1 year
measure: To determine the toxicity of amikacin
time frame: 1 year
measure: To investigate to what extend renal replacement therapy affects the pharmacokinetics of amikacin and cefuroxime
time frame: 1 year
arm group label: Cefuroxime/Amikacin
description: 20 patients will be included in the cefuroxime cohort and 20 patients in the amikacin cohort.
intervention type: Drug
intervention name: Cefuroxime
description: Patients receive cefuroxime as part of standard care.
arm group label: Cefuroxime/Amikacin
intervention type: Drug
intervention name: Amikacin
description: Patients receive amikacin as part of standard care.
arm group label: Cefuroxime/Amikacin
Blood samples and 24 hours urine will be collection following an intravenous gift of either
      cefuroxime or amikacin.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Roger Brüggemann, Phd
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Julian Machiels, MD, MSc
phone: +31243614369
email: julian.machiels@radboudumc.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Bacterial Infections
mesh term: Critical Illness
mesh term: Amikacin
mesh term: Cefuroxime
mesh term: Cefuroxime axetil
sharing ipd: Undecided