<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/NCT02240277</url>
  </required_header>
  <id_info>
    <org_study_id>RH-RBWH-2014-1</org_study_id>
    <secondary_id>2014-002555-26</secondary_id>
    <nct_id>NCT02240277</nct_id>
  </id_info>
  <brief_title>Meropenem and Ciprofloxacin Dosing in Septic Shock</brief_title>
  <official_title>Meropenem and Ciprofloxacin Dosing in the Critically Ill Patient With Septic Shock - a Single Center Pharmacokinetic Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The University of Queensland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with septic shock may have altered volume of distribution and metabolism of&#xD;
      antibiotics which are crucial medications for treating infections. The aim of the study is to&#xD;
      investigate the blood concentrations of Meropenem and Ciprofloxacin, two commonly used&#xD;
      antibiotics, in patients with septic shock. The hypothesis is that standard dosing may&#xD;
      produce insufficient levels of antibiotics in patients with septic shock.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sepsis may induce changes in renal function, increased capillary leakage and frequently&#xD;
      blood-flow stasis in the peripheral tissues leading to an increase in the water space and&#xD;
      diffusion distances. Significant changes have been observed in the distribution volume of&#xD;
      certain antibiotics in patients with sepsis. The increased volume of distribution of&#xD;
      water-soluble drugs is caused by a capillary leak syndrome that results in a net movement of&#xD;
      fluid from the intravascular compartment into tissues. This capillary leak syndrome has been&#xD;
      well described in patients with sepsis and may result in low trough serum concentrations.&#xD;
      This, in turn, may result in a slow antibiotic penetration of tissues and a low tissue&#xD;
      antibiotic concentration. Treatment failure may result if antibiotic choice or doses are&#xD;
      incorrect and there is a lack of information which describes how to alter drug dosing in&#xD;
      response to this increased volume of distribution in sepsis. Previous research has shown that&#xD;
      some intensive care unit (ICU) patients have larger than normal between subject variability&#xD;
      in drug clearance and volumes that can be attributed to supranormal renal clearances.&#xD;
&#xD;
      Aims of the present study:&#xD;
&#xD;
        1. To evaluate present meropenem and ciprofloxacin dosing and achieved plasma&#xD;
           concentrations in relation to bacterial susceptibility.&#xD;
&#xD;
        2. To evaluate how to accurately dose meropenem and ciprofloxacin in patients with sepsis&#xD;
           The overall hypothesis for this project is that some patients admitted to ICU with&#xD;
           severe sepsis are undertreated with meropenem and ciprofloxacin using the dosing based&#xD;
           on that recommended by the Product Information&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2014</start_date>
  <completion_date type="Anticipated">March 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2015</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>Area Under the Concentration-Time Curve (AUC 0-8h)</measure>
    <time_frame>Seven blood samples of 3 ml at T0 (pre dose), 30, 45, 60, 120, 240 and 480 mins post infusion completion.</time_frame>
    <description>The concentration versus time data for meropenem &amp; ciprofloxacin in plasma will be analysed by a non-linear mixed effects modelling approach using NONMEM (Version 7.3, GloboMax LLC, Hanover, MD, USA) with double precision with the COMPAQ VISUAL FORTRAN compiler</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Septic Shock</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients admitted to ICU with septic shock treated with the study drugs, initiated at the&#xD;
        discretion of the treating doctor.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years and &lt;90 years&#xD;
&#xD;
          -  Clinical indication for therapy of one of the study antibiotics Meropenem or&#xD;
             Ciprofloxacin in patients diagnosed at or during admission to ICU with septic shock&#xD;
&#xD;
          -  Sepsis will be defined as:&#xD;
&#xD;
               -  Clinical suspicion of infection and/or Positive culture results&#xD;
&#xD;
               -  Systemic inflammatory response syndrome (SIRS) as defined by 2 or more of the&#xD;
                  following:&#xD;
&#xD;
               -  Core temperature &lt; 36o C or &gt; 38o C&#xD;
&#xD;
               -  Tachycardia as defined by a heart rate &gt; 90 beats per minute&#xD;
&#xD;
               -  Tachypnoea as defined by a respiratory rate greater than 20 breaths per minute OR&#xD;
                  a PaCO2 less than 32 mmHg during spontaneous ventilation OR the requirement for&#xD;
                  mechanical ventilation.&#xD;
&#xD;
               -  A white blood cell count &gt; 12 X 109 / L OR &lt; 4 X 109 / L OR greater than 10 %&#xD;
                  immature (band) forms.&#xD;
&#xD;
          -  Septic shock will be defined as:&#xD;
&#xD;
               -  Sepsis with persistent hypotension, systolic blood pressure &lt; 90 mmHg or mean&#xD;
                  arterial pressure &lt; 65 despite adequate fluid resuscitation&#xD;
&#xD;
               -  Requirement of inotropic support.&#xD;
&#xD;
          -  Normal renal function as defined by:&#xD;
&#xD;
               -  Serum creatinine &lt;170 mmol/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing renal impairment as defined by:&#xD;
&#xD;
               -  Serum creatinine above normal limits ( defined as &gt;500mmol/L)&#xD;
&#xD;
                    -  Need for renal replacement therapy&#xD;
&#xD;
                    -  History of allergy to study antibiotic&#xD;
&#xD;
                    -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fredrik Sjoevall, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fredrik Sjoevall, MD PhD</last_name>
    <phone>+4535450554</phone>
    <email>ksjo0001@regionh.dk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>September 11, 2014</last_update_submitted>
  <last_update_submitted_qc>September 11, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Fredrik Sjövall</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Septic Shock</keyword>
  <keyword>Meropenem</keyword>
  <keyword>Ciprofloxacin</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Shock</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/NCT02240277
org study id: RH-RBWH-2014-1
secondary id: 2014-002555-26
nct id: NCT02240277
lead sponsor: 
collaborator: 
has dmc: Yes
Patients with septic shock may have altered volume of distribution and metabolism of
      antibiotics which are crucial medications for treating infections. The aim of the study is to
      investigate the blood concentrations of Meropenem and Ciprofloxacin, two commonly used
      antibiotics, in patients with septic shock. The hypothesis is that standard dosing may
      produce insufficient levels of antibiotics in patients with septic shock.
Sepsis may induce changes in renal function, increased capillary leakage and frequently
      blood-flow stasis in the peripheral tissues leading to an increase in the water space and
      diffusion distances. Significant changes have been observed in the distribution volume of
      certain antibiotics in patients with sepsis. The increased volume of distribution of
      water-soluble drugs is caused by a capillary leak syndrome that results in a net movement of
      fluid from the intravascular compartment into tissues. This capillary leak syndrome has been
      well described in patients with sepsis and may result in low trough serum concentrations.
      This, in turn, may result in a slow antibiotic penetration of tissues and a low tissue
      antibiotic concentration. Treatment failure may result if antibiotic choice or doses are
      incorrect and there is a lack of information which describes how to alter drug dosing in
      response to this increased volume of distribution in sepsis. Previous research has shown that
      some intensive care unit (ICU) patients have larger than normal between subject variability
      in drug clearance and volumes that can be attributed to supranormal renal clearances.

      Aims of the present study:

        1. To evaluate present meropenem and ciprofloxacin dosing and achieved plasma
           concentrations in relation to bacterial susceptibility.

        2. To evaluate how to accurately dose meropenem and ciprofloxacin in patients with sepsis
           The overall hypothesis for this project is that some patients admitted to ICU with
           severe sepsis are undertreated with meropenem and ciprofloxacin using the dosing based
           on that recommended by the Product Information
observational model: Cohort
time perspective: Prospective
measure: Area Under the Concentration-Time Curve (AUC 0-8h)
time frame: Seven blood samples of 3 ml at T0 (pre dose), 30, 45, 60, 120, 240 and 480 mins post infusion completion.
description: The concentration versus time data for meropenem & ciprofloxacin in plasma will be analysed by a non-linear mixed effects modelling approach using NONMEM (Version 7.3, GloboMax LLC, Hanover, MD, USA) with double precision with the COMPAQ VISUAL FORTRAN compiler
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Fredrik Sjoevall, MD, PhD
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
last name: Fredrik Sjoevall, MD PhD
phone: +4535450554
email: ksjo0001@regionh.dk
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Fredrik Sjövall
investigator title: MD, PhD
mesh term: Shock, Septic
mesh term: Shock