<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/NCT03798600</url>
  </required_header>
  <id_info>
    <org_study_id>CEAVC, 32366/2015; OSS.15.114</org_study_id>
    <nct_id>NCT03798600</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics/Pharmacodynamics (PK/PD) of Caspofungin in Intensive Care Unit (ICU) Patients. An Open Observational Study for Antifungal Treatment's Optimization</brief_title>
  <official_title>Pharmacokinetics/Pharmacodynamics (PK/PD) of Caspofungin in Intensive Care Unit (ICU) Patients. An Open Observational Study for Antifungal Treatment's Optimization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Careggi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Careggi Hospital</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>
      PK of Caspofungin in ICU septic patients might be changed as compared to healthy volunteers&#xD;
      due to sepsis-related pathophysiology.&#xD;
&#xD;
      Sub-optimal plasma and tissue concentrations might be achieved in these patients when drugs&#xD;
      are administered at the same dosage/regimen suggested for healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open non randomized, non controlled single center study on the pharmacokinetics of&#xD;
      caspofungin in 20 consecutive ICU patients with severe sepsis or septic shock, requiring&#xD;
      caspofungin therapy and PK-PD evaluation for the optimization of caspofungin therapy. The aim&#xD;
      of this study is to describe the Caspofungin PK-PD alterations in a cohort of critically ill&#xD;
      septic patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2016</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</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>Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>first 24 hours after loading dose</time_frame>
    <description>The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).</measure>
    <time_frame>at day 4 after loading dose</time_frame>
    <description>The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">20</enrollment>
  <condition>Critical Illness</condition>
  <condition>Infection</condition>
  <arm_group>
    <arm_group_label>Critically ill patients</arm_group_label>
    <description>20 patients consecutively admitted in the ICU with severe sepsis or septic shock requiring caspofungin therapy will be considered for this observational study.&#xD;
Inclusion Criteria:&#xD;
Adult ICU patients (&gt;18 yrs) with severe sepsis or septic shock undergoing caspofungin therapy based on clinical judgement (empiric therapy) or microbiological result (targeted therapy).&#xD;
Exclusion criteria:&#xD;
Concomitant ciclosporin or rifampicin therapy. Pregnancy Continuous renal replacement therapy Severe Liver failure (Child Pugh score &gt; 6)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Caspofungin</intervention_name>
    <description>In accordance with routine clinical practice, Caspofungin will be given at the loading dose of 70 mg followed by 50 mg daily (for people &lt; 80 kg body weight). No dose reduction will be performed in Child-Pugh score A or B. Duration of therapy will be performed in accordance with ESCMID guidelines and clinical conditions.</description>
    <arm_group_label>Critically ill patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum and urine samples. To perform the PK study, blood samples (of approximately 2 ml each)&#xD;
      will be obtained at different time points following the first administration. These samples&#xD;
      will occur at the same time of routine blood gas analysis (hourly obtained in the ICU) and no&#xD;
      further extra-routine blood samples will be required for this study. In particular, the blood&#xD;
      that normally remains in the syringe of blood gas analysis, and usually thrown as waste&#xD;
      fluid, will be saved and used for PK analysis. Thus, no increase in blood sampling from the&#xD;
      patient will be obtained, both in terms of frequency of sampling or volume of blood.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        20 patients consecutively admitted in the ICU with severe sepsis or septic shock requiring&#xD;
        caspofungin therapy will be considered for this observational study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult ICU patients (&gt;18 yrs)&#xD;
&#xD;
          -  Severe sepsis or septic shock&#xD;
&#xD;
          -  Caspofungin therapy based on clinical judgement (empiric therapy) or microbiological&#xD;
             result (targeted therapy).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant ciclosporin or rifampicin therapy.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Continuous renal replacement therapy&#xD;
&#xD;
          -  Severe Liver failure (Child Pugh score &gt; 6)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gianluca Villa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Careggi</affiliation>
  </overall_official>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Careggi Hospital</investigator_affiliation>
    <investigator_full_name>Gianluca Villa</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Caspofungin</keyword>
  <keyword>pharmacokinetic</keyword>
  <keyword>pharmacodynamic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Caspofungin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03798600
org study id: CEAVC, 32366/2015; OSS.15.114
nct id: NCT03798600
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
PK of Caspofungin in ICU septic patients might be changed as compared to healthy volunteers
      due to sepsis-related pathophysiology.

      Sub-optimal plasma and tissue concentrations might be achieved in these patients when drugs
      are administered at the same dosage/regimen suggested for healthy volunteers.
Open non randomized, non controlled single center study on the pharmacokinetics of
      caspofungin in 20 consecutive ICU patients with severe sepsis or septic shock, requiring
      caspofungin therapy and PK-PD evaluation for the optimization of caspofungin therapy. The aim
      of this study is to describe the Caspofungin PK-PD alterations in a cohort of critically ill
      septic patients.
observational model: Cohort
time perspective: Prospective
measure: Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).
time frame: first 24 hours after loading dose
description: The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.
measure: Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
time frame: first 24 hours after loading dose
description: The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.
measure: Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
time frame: at day 4 after loading dose
description: The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.
measure: Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
time frame: first 24 hours after loading dose
description: The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.
measure: Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
time frame: at day 4 after loading dose
description: The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.
measure: Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
time frame: first 24 hours after loading dose
description: The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
time frame: at day 4 after loading dose
description: The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
time frame: first 24 hours after loading dose
description: The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
time frame: at day 4 after loading dose
description: The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).
time frame: first 24 hours after loading dose
description: The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).
time frame: at day 4 after loading dose
description: The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).
time frame: first 24 hours after loading dose
description: The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).
time frame: at day 4 after loading dose
description: The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers.
measure: Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).
time frame: at day 4 after loading dose
description: The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.
arm group label: Critically ill patients
description: 20 patients consecutively admitted in the ICU with severe sepsis or septic shock requiring caspofungin therapy will be considered for this observational study.
Inclusion Criteria:
Adult ICU patients (>18 yrs) with severe sepsis or septic shock undergoing caspofungin therapy based on clinical judgement (empiric therapy) or microbiological result (targeted therapy).
Exclusion criteria:
Concomitant ciclosporin or rifampicin therapy. Pregnancy Continuous renal replacement therapy Severe Liver failure (Child Pugh score > 6)
intervention type: Drug
intervention name: Caspofungin
description: In accordance with routine clinical practice, Caspofungin will be given at the loading dose of 70 mg followed by 50 mg daily (for people < 80 kg body weight). No dose reduction will be performed in Child-Pugh score A or B. Duration of therapy will be performed in accordance with ESCMID guidelines and clinical conditions.
arm group label: Critically ill patients
Serum and urine samples. To perform the PK study, blood samples (of approximately 2 ml each)
      will be obtained at different time points following the first administration. These samples
      will occur at the same time of routine blood gas analysis (hourly obtained in the ICU) and no
      further extra-routine blood samples will be required for this study. In particular, the blood
      that normally remains in the syringe of blood gas analysis, and usually thrown as waste
      fluid, will be saved and used for PK analysis. Thus, no increase in blood sampling from the
      patient will be obtained, both in terms of frequency of sampling or volume of blood.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Gianluca Villa, MD
role: Principal Investigator
affiliation: Azienda Careggi
responsible party type: Principal Investigator
investigator affiliation: Careggi Hospital
investigator full name: Gianluca Villa
investigator title: Principal investigator
mesh term: Critical Illness
mesh term: Caspofungin
sharing ipd: No