<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/NCT02242006</url>
  </required_header>
  <id_info>
    <org_study_id>20140429</org_study_id>
    <nct_id>NCT02242006</nct_id>
  </id_info>
  <brief_title>Antimicrobial Pharmacokinetics in Critically Ill Adults During Sustained Low Efficiency Dialysis (SLED)</brief_title>
  <official_title>Antimicrobial Pharmacokinetics in Critically Ill Adults During Sustained Low Efficiency Dialysis (SLED)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</source>
  <brief_summary>
    <textblock>
      Severe acute kidney injury (AKI) is a common complication of critical illness affecting&#xD;
      almost half of all patients with septic shock. Extracorporeal renal replacement therapy is a&#xD;
      cornerstone in the management of AKI in these patients. Options for renal replacement therapy&#xD;
      include continuous renal replacement (CRRT) therapy, intermittent dialysis (IHD) or a hybrid&#xD;
      form of the two called sustained low efficiency dialysis (SLED). Globally there is a push to&#xD;
      switch from traditional CRRT to SLED. Although there are resource and financial comparative&#xD;
      benefits to SLED there is almost no literature describing how to dose antimicrobials (or&#xD;
      other drugs for that matter). It appears that drug clearance on SLED may be more efficient&#xD;
      than CRRT but not as efficient as IHD making extrapolation from these bodies of literature&#xD;
      inappropriate for SLED. The investigators are proposing to conduct the population&#xD;
      pharmacokinetic studies for the three most commonly used antimicrobials in critically ill&#xD;
      patients receiving SLED therapy (piperacillin-tazobactam, meropenem and vancomycin).&#xD;
      Population pharmacokinetic modeling of these drugs will provide estimates and sources of&#xD;
      variability around pharmacokinetic parameters that will subsequently be used for Monte Carlo&#xD;
      simulation to determine the most appropriate dosing regimens to achieve therapeutic targets&#xD;
      while minimizing the risk of toxicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>drug clearance</measure>
    <time_frame>During the first run of SLED after study inclusion</time_frame>
    <description>Serial serum samples will be obtained after drug administration and during SLED to determine drug clearance during SLED.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>volume of distribution</measure>
    <time_frame>During the first run of SLED after study inclusion</time_frame>
    <description>Serial serum samples will be obtained after drug administration and during SLED to determine drug volume of distribition during SLED.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">90</enrollment>
  <condition>Critical Illness</condition>
  <condition>Kidney Injury</condition>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>piperacillin/tazobactam</arm_group_label>
    <description>Serial serum sampling of patients receiving piperacillin/tazobactam and SLED simultaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>meropenem</arm_group_label>
    <description>Serial serum sampling of patients receiving meropenem and SLED simultaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>vancomycin</arm_group_label>
    <description>Serial serum sampling of patients receiving vancomycin and SLED simultaneously</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>serial serum sampling for quantification of drug concentration</intervention_name>
    <arm_group_label>meropenem</arm_group_label>
    <arm_group_label>piperacillin/tazobactam</arm_group_label>
    <arm_group_label>vancomycin</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        critically ill adults admitted to an ICU&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Critically ill adults [age ≥ 18] admitted to one of two of the medical/surgical&#xD;
             intensive care units (ICUs) of The Ottawa Hospital, who require SLED and are or will&#xD;
             receive meropenem, piperacillin-tazobactam or vancomycin therapy at any dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients for whom participation via the informed consent process is denied.&#xD;
&#xD;
          -  Critically ill patients with a hypermetabolic state due to &gt;25% coverage of body&#xD;
             surface area burn, cystic fibrosis, spinal cord injury, bariatric patients (defined as&#xD;
             &gt;150kg total body weight)&#xD;
&#xD;
          -  Patient is pregnant as per a positive serum or urine βHCG qualitative assay&#xD;
&#xD;
          -  Patient does not have a closed-system arterial or central venous catheter (to minimize&#xD;
             blood wastage)&#xD;
&#xD;
          -  Patients receiving concomitant drugs known to interact with the metabolism or&#xD;
             clearance of the antimicrobial of interest according to Micromedex 2.0 (Truven Health&#xD;
             Analytics Inc 2013)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <!-- 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/NCT02242006
org study id: 20140429
nct id: NCT02242006
lead sponsor: 
Severe acute kidney injury (AKI) is a common complication of critical illness affecting
      almost half of all patients with septic shock. Extracorporeal renal replacement therapy is a
      cornerstone in the management of AKI in these patients. Options for renal replacement therapy
      include continuous renal replacement (CRRT) therapy, intermittent dialysis (IHD) or a hybrid
      form of the two called sustained low efficiency dialysis (SLED). Globally there is a push to
      switch from traditional CRRT to SLED. Although there are resource and financial comparative
      benefits to SLED there is almost no literature describing how to dose antimicrobials (or
      other drugs for that matter). It appears that drug clearance on SLED may be more efficient
      than CRRT but not as efficient as IHD making extrapolation from these bodies of literature
      inappropriate for SLED. The investigators are proposing to conduct the population
      pharmacokinetic studies for the three most commonly used antimicrobials in critically ill
      patients receiving SLED therapy (piperacillin-tazobactam, meropenem and vancomycin).
      Population pharmacokinetic modeling of these drugs will provide estimates and sources of
      variability around pharmacokinetic parameters that will subsequently be used for Monte Carlo
      simulation to determine the most appropriate dosing regimens to achieve therapeutic targets
      while minimizing the risk of toxicity.
observational model: Cohort
time perspective: Prospective
measure: drug clearance
time frame: During the first run of SLED after study inclusion
description: Serial serum samples will be obtained after drug administration and during SLED to determine drug clearance during SLED.
measure: volume of distribution
time frame: During the first run of SLED after study inclusion
description: Serial serum samples will be obtained after drug administration and during SLED to determine drug volume of distribition during SLED.
arm group label: piperacillin/tazobactam
description: Serial serum sampling of patients receiving piperacillin/tazobactam and SLED simultaneously
arm group label: meropenem
description: Serial serum sampling of patients receiving meropenem and SLED simultaneously
arm group label: vancomycin
description: Serial serum sampling of patients receiving vancomycin and SLED simultaneously
intervention type: Other
intervention name: serial serum sampling for quantification of drug concentration
arm group label: meropenem
arm group label: piperacillin/tazobactam
arm group label: vancomycin
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Critical Illness