<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/NCT01666769</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00039552</org_study_id>
    <nct_id>NCT01666769</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation</brief_title>
  <official_title>Safety and Pharmacokinetics of Micafungin in Children Supported With Extracorporeal Membrane Oxygenation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kevin Watt</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine proper dosing of micafungin in children supported with extracorporeal membrane&#xD;
      oxygenation (ECMO).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that provides&#xD;
      life-saving, complete respiratory and cardiac support for children who suffer refractory&#xD;
      heart or lung failure. While on ECMO, children are at increased risk of infection, including&#xD;
      fungal infection. Antifungal prophylaxis can potentially reduce the burden of disease in&#xD;
      children on ECMO. Because fungal infections can result in biofilms that are difficult to&#xD;
      treat, treatment includes not only antifungal medications but also removal of any large&#xD;
      intravenous lines. However, catheter removal for children on ECMO is impossible; therefore,&#xD;
      therapy relies upon optimal antifungal management alone.&#xD;
&#xD;
      Micafungin is an antifungal medication that works well against the most common fungal&#xD;
      infections and has been shown to be safe in children. Micafungin may be particularly&#xD;
      efficacious in children on ECMO because of the drug's ability to penetrate biofilms. However,&#xD;
      the ECMO circuit is known to substantially alter drug levels for many drugs, resulting in&#xD;
      important dosing changes. Appropriate micafungin dosing in this setting is unknown and&#xD;
      sub-optimal dosing might result in therapeutic and prophylactic failure.&#xD;
&#xD;
      Standard dosing of micafungin are 4 and 2 mg per kilogram of body weight given intravenously&#xD;
      once daily for treatment and prophylaxis, respectively. Based on preliminary data and&#xD;
      modeling from other studies, investigators hypothesize that 8 and 4 mg per kilogram given&#xD;
      once daily will achieve proper drug levels to respectively treat and prevent fungal&#xD;
      infections in children under 2 years of age who are supported by ECMO. Because the ECMO&#xD;
      circuit should have less of an impact on volume of distribution in larger children,&#xD;
      investigators hypothesize that in children from 2 to 18 years old, standard dosing of&#xD;
      micafungin will achieve proper drug concentrations.&#xD;
&#xD;
      Investigators hold the FDA investigational new drug application (IND #115255) to give&#xD;
      micafungin to children on ECMO at the doses described above. Blood samples will be collected&#xD;
      at specific times around the first and fourth micafungin doses to describe the&#xD;
      pharmacokinetics and drug extraction by the ECMO circuit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">February 9, 2016</completion_date>
  <primary_completion_date type="Actual">February 2, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic primary endpoints</measure>
    <time_frame>Around the first and fourth doses of micafungin: 0-4h prior to and 0-30 min, 60-90 min, 2-4h, 8-10h, 12-16h, 22-24h after infusion of study drug</time_frame>
    <description>Clearance rate (CL), Volume of distribution (V), Oxygenator extraction efficacy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>From Dose 1 until 7 days after the last dose</time_frame>
    <description>Number of adverse events (any untoward medical occurrence in humans, whether or not considered drug-related, which occurs during the conduct of a clinical trial)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Invasive Candidiasis</condition>
  <arm_group>
    <arm_group_label>Treatment Dosing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Age group: 0 - &lt;2y, Micafungin 8 mg/kg/day IV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prophylaxis dosing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Age group: 0-&lt;2y, Micafungin 4 mg/kg/day IV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care Dosing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Micafungin</intervention_name>
    <description>4 mg/kg/day</description>
    <arm_group_label>Prophylaxis dosing</arm_group_label>
    <other_name>Mycamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Micafungin</intervention_name>
    <description>8 mg/kg/day</description>
    <arm_group_label>Treatment Dosing</arm_group_label>
    <other_name>Mycamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Micafungin</intervention_name>
    <description>Standard of care Dosing</description>
    <arm_group_label>Standard of care Dosing</arm_group_label>
    <other_name>Mycamine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &lt;= 17.85 years at the time of enrollment.&#xD;
&#xD;
          -  Sufficient venous access to permit administration of study medication.&#xD;
&#xD;
          -  Supported with either venoarterial (VA) or venovenous (VV) ECMO.&#xD;
&#xD;
          -  Availability and willingness of the parent/legal guardian to provide written informed&#xD;
             consent.&#xD;
&#xD;
          -  For treatment dosing arm: confirmed or suspected infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject with a history of anaphylaxis attributed to an echinocandin.&#xD;
&#xD;
          -  Any other concomitant condition, which in the opinion of the investigator would&#xD;
             preclude a subject's participation in the study.&#xD;
&#xD;
          -  Previous participation in this study.&#xD;
&#xD;
          -  Pregnancy&#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>Kevin Watt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Clinical Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>November 1, 2019</last_update_submitted>
  <last_update_submitted_qc>November 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Kevin Watt</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Extracorporeal membrane oxygenation</keyword>
  <keyword>ECMO</keyword>
  <keyword>Extracorporeal life support</keyword>
  <keyword>Micafungin</keyword>
  <keyword>Mycamine</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Candidiasis</mesh_term>
    <mesh_term>Candidiasis, Invasive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Micafungin</mesh_term>
  </intervention_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/NCT01666769
org study id: Pro00039552
nct id: NCT01666769
lead sponsor: 
has dmc: No
Determine proper dosing of micafungin in children supported with extracorporeal membrane
      oxygenation (ECMO).
Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that provides
      life-saving, complete respiratory and cardiac support for children who suffer refractory
      heart or lung failure. While on ECMO, children are at increased risk of infection, including
      fungal infection. Antifungal prophylaxis can potentially reduce the burden of disease in
      children on ECMO. Because fungal infections can result in biofilms that are difficult to
      treat, treatment includes not only antifungal medications but also removal of any large
      intravenous lines. However, catheter removal for children on ECMO is impossible; therefore,
      therapy relies upon optimal antifungal management alone.

      Micafungin is an antifungal medication that works well against the most common fungal
      infections and has been shown to be safe in children. Micafungin may be particularly
      efficacious in children on ECMO because of the drug's ability to penetrate biofilms. However,
      the ECMO circuit is known to substantially alter drug levels for many drugs, resulting in
      important dosing changes. Appropriate micafungin dosing in this setting is unknown and
      sub-optimal dosing might result in therapeutic and prophylactic failure.

      Standard dosing of micafungin are 4 and 2 mg per kilogram of body weight given intravenously
      once daily for treatment and prophylaxis, respectively. Based on preliminary data and
      modeling from other studies, investigators hypothesize that 8 and 4 mg per kilogram given
      once daily will achieve proper drug levels to respectively treat and prevent fungal
      infections in children under 2 years of age who are supported by ECMO. Because the ECMO
      circuit should have less of an impact on volume of distribution in larger children,
      investigators hypothesize that in children from 2 to 18 years old, standard dosing of
      micafungin will achieve proper drug concentrations.

      Investigators hold the FDA investigational new drug application (IND #115255) to give
      micafungin to children on ECMO at the doses described above. Blood samples will be collected
      at specific times around the first and fourth micafungin doses to describe the
      pharmacokinetics and drug extraction by the ECMO circuit.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic primary endpoints
time frame: Around the first and fourth doses of micafungin: 0-4h prior to and 0-30 min, 60-90 min, 2-4h, 8-10h, 12-16h, 22-24h after infusion of study drug
description: Clearance rate (CL), Volume of distribution (V), Oxygenator extraction efficacy
measure: Safety
time frame: From Dose 1 until 7 days after the last dose
description: Number of adverse events (any untoward medical occurrence in humans, whether or not considered drug-related, which occurs during the conduct of a clinical trial)
arm group label: Treatment Dosing
arm group type: Other
description: Age group: 0 - <2y, Micafungin 8 mg/kg/day IV
arm group label: Prophylaxis dosing
arm group type: Other
description: Age group: 0-<2y, Micafungin 4 mg/kg/day IV
arm group label: Standard of care Dosing
arm group type: Other
description: Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)
intervention type: Drug
intervention name: Micafungin
description: 4 mg/kg/day
arm group label: Prophylaxis dosing
other name: Mycamine
intervention type: Drug
intervention name: Micafungin
description: 8 mg/kg/day
arm group label: Treatment Dosing
other name: Mycamine
intervention type: Drug
intervention name: Micafungin
description: Standard of care Dosing
arm group label: Standard of care Dosing
other name: Mycamine
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Kevin Watt, MD
role: Principal Investigator
affiliation: Duke Clinical Research Institute
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Kevin Watt
investigator title: Assistant Professor
mesh term: Candidiasis
mesh term: Candidiasis, Invasive
mesh term: Micafungin