<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/NCT02220790</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00056090</org_study_id>
    <nct_id>NCT02220790</nct_id>
  </id_info>
  <brief_title>BIOPIC: Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric Candidemia</brief_title>
  <acronym>BIOPIC</acronym>
  <official_title>Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to 1) define the operating characteristics of fungal biomarker&#xD;
      assays in pediatric patients at high-risk for developing invasive candidiasis, 2) determine&#xD;
      the change in fungal biomarker assay results in children who develop invasive candidiasis,&#xD;
      and 3) create a biobank of blood samples from pediatric patients at high-risk for invasive&#xD;
      candidiasis and those with invasive candidiasis for future testing of fungal biomarker assays&#xD;
      and development of new fungal biomarker assays. The study will assemble a prospective cohort&#xD;
      of pediatric patients at high-risk for developing invasive candidiasis. Blood samples for&#xD;
      biomarker testing will be obtained at the time a patient has a clinical indication for blood&#xD;
      culture attainment. Additional blood sampling will be performed on the sub-set of patients&#xD;
      that are found to have invasive candidiasis. The sensitivity, specificity, PPV, and NPV of&#xD;
      biomarker assays will be determined for each biomarker assay. No PHI will be stored in the&#xD;
      database and limits on blood draws (3 ml/kg in an 8 week period) will be adhered to.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will create an international multi-center cohort of children with new clinical&#xD;
      concern for infection while in the hospital. Sites used are part of the International&#xD;
      Pediatric Fungal Network (ipfn.org). The study plans to prospectively enroll pediatric&#xD;
      patients at high-risk of developing invasive candidiasis over a four year period. The study&#xD;
      duration per subject will be up to 14 days for blood collection and 30 days for data&#xD;
      collection from the medical record.&#xD;
&#xD;
      For the first aim, this study will assemble a prospective cohort of pediatric patients at&#xD;
      high-risk for developing invasive candidiasis. Blood samples for biomarker testing will be&#xD;
      obtained within 24-hours of a patient having a clinical indication for blood culture&#xD;
      attainment. To accomplish the second aim, additional blood sampling will be performed in the&#xD;
      sub-set of patients that are found to have invasive candidiasis. For the third aim, remnant&#xD;
      blood samples following biomarker testing from all consenting participants will be stored in&#xD;
      a biobank. This biobank will be used to examine future, currently undeveloped, biomarker&#xD;
      assays in an effort to further reduce the time to diagnosis of invasive candidiasis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">October 8, 2020</completion_date>
  <primary_completion_date type="Actual">October 8, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>30 Days</target_duration>
  <primary_outcome>
    <measure>NPV, PPV, sensitivity, specificity, and threshold for positive result of fungal biomarker assays</measure>
    <time_frame>1 day</time_frame>
    <description>Operating characteristics of fungal biomarker assays in pediatric patients at high-risk for developing invasive candidiasis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in fungal biomarker assay results</measure>
    <time_frame>14 days</time_frame>
    <description>Measure the change in fungal biomarker assay results in those children who developed invasive candidiasis in order to monitor their response to therapy</description>
  </secondary_outcome>
  <enrollment type="Actual">515</enrollment>
  <condition>Invasive Candidiasis</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This study will create an international multi-center cohort of children with new clinical&#xD;
        concern for infection while in the hospital.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females age &gt; 120 days and &lt;18 years&#xD;
&#xD;
          2. Have at least one of the following conditions:&#xD;
&#xD;
               -  admitted to a non-neonatal ICU with any underlying disease&#xD;
&#xD;
               -  being transferred imminently to a non-neonatal ICU with any underlying disease&#xD;
&#xD;
               -  have gastro-intestinal insufficiency (eg. chronic short-gut syndrome) and&#xD;
                  admitted to anywhere in the hospital&#xD;
&#xD;
               -  have a hematological malignancy (limited to AML, ALL, non-Hodgkin's lymphoma and&#xD;
                  myelodysplastic syndrome) and admitted to anywhere to the hospital&#xD;
&#xD;
               -  have a solid tumor malignancy and admitted to anywhere in the hospital&#xD;
&#xD;
               -  have a solid organ transplant and be admitted to anywhere in the hospital&#xD;
&#xD;
               -  have a hemopoietic stem cell or bone marrow transplant and be admitted to&#xD;
                  anywhere in the hospital&#xD;
&#xD;
               -  have aplastic anemia and be admitted to anywhere in the hospital&#xD;
&#xD;
          3. Have ≥ 1 central catheter (arterial or venous)&#xD;
&#xD;
          4. Have ≥ 1 blood culture drawn for clinical concern of infection at time of enrollment&#xD;
&#xD;
          5. Clinician initiates and/or changes any systemic antimicrobial therapy at time of&#xD;
             enrollment&#xD;
&#xD;
          6. Parental/guardian permission (informed consent) and, if appropriate, child assent.&#xD;
&#xD;
          7. For Aim 2: Each of the above AND a positive blood culture or sterile site culture for&#xD;
             Candida spp. that turns positive between day 0 and day +14.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of an invasive fungal disease within the 30 days prior to the blood culture&#xD;
             drawn of clinical concern of infection.&#xD;
&#xD;
          2. Previous inclusion in this study&#xD;
&#xD;
          3. Weight &lt; 4 kg (Due to constraints of no more than 3 ml/kg of blood to be drawn over an&#xD;
             8 week period). Subjects that fall below 4 kg during the study period that blood draws&#xD;
             are occurring will not have more than 0.75 ml/kg of blood drawn each time.&#xD;
&#xD;
          4. Patient receiving empiric anti-fungal therapy for prolonged neutropenia or fever that&#xD;
             was started prior to the time of blood culture&#xD;
&#xD;
          5. If blood cultures obtained and anti-infectives are added/changed only as part of a&#xD;
             local protocol and not dictated by clinical concern of infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>120 Days</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William J Steinbach, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brian T Fisher, DO, MPH, MSCE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arkansas Children's Hospital</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>All Children's Hospital</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann and Robert Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cohen Children's Medical Center of New York</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York-Presbyterian Phyllis and David Komansky Center for Children's Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Children's</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dell Children's Medical Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>3rd Department Pediatrics Aristole University School of Medicine, Hippokration Hospital</name>
      <address>
        <city>Thessaloniki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Faisal Specialist Hospital and Research Center</name>
      <address>
        <city>Riyadh</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital d'Unverisitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>Saudi Arabia</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Fisher BT, Boge CLK, Xiao R, Shuster S, Chin-Quee D, Allen J, Shaheen S, Hayden R, Suganda S, Zaoutis TE, Chang YC, Yin DE, Huppler AR, Danziger-Isakov L, Muller WJ, Roilides E, Romero J, Sue PK, Berman D, Wattier RL, Halasa N, Pong A, Maron G, Soler-Palacin P, Hutto SC, Gonzalez BE, Salvatore CM, Rajan S, Green M, Doby Knackstedt E, Hauger SB, Steinbach WJ. Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents. Clin Infect Dis. 2022 Aug 25;75(2):248-259. doi: 10.1093/cid/ciab928. Erratum In: Clin Infect Dis. 2023 Mar 4;76(5):972.</citation>
    <PMID>35134165</PMID>
  </results_reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>February 10, 2022</last_update_submitted>
  <last_update_submitted_qc>February 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IPFN</keyword>
  <keyword>Pediatric</keyword>
  <keyword>Fungal</keyword>
  <keyword>Biomarker Assays</keyword>
  <keyword>Candida</keyword>
  <keyword>Pediatric ICU patient</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>
  <!-- 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/NCT02220790
org study id: Pro00056090
nct id: NCT02220790
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of the study is to 1) define the operating characteristics of fungal biomarker
      assays in pediatric patients at high-risk for developing invasive candidiasis, 2) determine
      the change in fungal biomarker assay results in children who develop invasive candidiasis,
      and 3) create a biobank of blood samples from pediatric patients at high-risk for invasive
      candidiasis and those with invasive candidiasis for future testing of fungal biomarker assays
      and development of new fungal biomarker assays. The study will assemble a prospective cohort
      of pediatric patients at high-risk for developing invasive candidiasis. Blood samples for
      biomarker testing will be obtained at the time a patient has a clinical indication for blood
      culture attainment. Additional blood sampling will be performed on the sub-set of patients
      that are found to have invasive candidiasis. The sensitivity, specificity, PPV, and NPV of
      biomarker assays will be determined for each biomarker assay. No PHI will be stored in the
      database and limits on blood draws (3 ml/kg in an 8 week period) will be adhered to.
This study will create an international multi-center cohort of children with new clinical
      concern for infection while in the hospital. Sites used are part of the International
      Pediatric Fungal Network (ipfn.org). The study plans to prospectively enroll pediatric
      patients at high-risk of developing invasive candidiasis over a four year period. The study
      duration per subject will be up to 14 days for blood collection and 30 days for data
      collection from the medical record.

      For the first aim, this study will assemble a prospective cohort of pediatric patients at
      high-risk for developing invasive candidiasis. Blood samples for biomarker testing will be
      obtained within 24-hours of a patient having a clinical indication for blood culture
      attainment. To accomplish the second aim, additional blood sampling will be performed in the
      sub-set of patients that are found to have invasive candidiasis. For the third aim, remnant
      blood samples following biomarker testing from all consenting participants will be stored in
      a biobank. This biobank will be used to examine future, currently undeveloped, biomarker
      assays in an effort to further reduce the time to diagnosis of invasive candidiasis.
observational model: Cohort
time perspective: Prospective
measure: NPV, PPV, sensitivity, specificity, and threshold for positive result of fungal biomarker assays
time frame: 1 day
description: Operating characteristics of fungal biomarker assays in pediatric patients at high-risk for developing invasive candidiasis
measure: change in fungal biomarker assay results
time frame: 14 days
description: Measure the change in fungal biomarker assay results in those children who developed invasive candidiasis in order to monitor their response to therapy
Blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 120 Days
maximum age: 18 Years
healthy volunteers: No
last name: William J Steinbach, MD
role: Principal Investigator
affiliation: Duke University
last name: Brian T Fisher, DO, MPH, MSCE
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
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country: Greece
country: Saudi Arabia
country: Spain
country: United States
citation: Fisher BT, Boge CLK, Xiao R, Shuster S, Chin-Quee D, Allen J, Shaheen S, Hayden R, Suganda S, Zaoutis TE, Chang YC, Yin DE, Huppler AR, Danziger-Isakov L, Muller WJ, Roilides E, Romero J, Sue PK, Berman D, Wattier RL, Halasa N, Pong A, Maron G, Soler-Palacin P, Hutto SC, Gonzalez BE, Salvatore CM, Rajan S, Green M, Doby Knackstedt E, Hauger SB, Steinbach WJ. Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents. Clin Infect Dis. 2022 Aug 25;75(2):248-259. doi: 10.1093/cid/ciab928. Erratum In: Clin Infect Dis. 2023 Mar 4;76(5):972.
PMID: 35134165
responsible party type: Sponsor
mesh term: Candidiasis
mesh term: Candidiasis, Invasive