<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/NCT01683370</url>
  </required_header>
  <id_info>
    <org_study_id>PFND2012B</org_study_id>
    <secondary_id>KFS-2933-02-2012</secondary_id>
    <nct_id>NCT01683370</nct_id>
  </id_info>
  <brief_title>Pediatric FN Definition 2012 Bern</brief_title>
  <official_title>Pediatric FN Definition 2012 Bern The Impact of Lowering Fever Limits on the Rate of Fever in Chemotherapy-induced Neutropenia (FN). A Prospective Single-center Observational Study in Children and Adolescents With Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Roland Ammann</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swiss Cancer League</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Swiss Pediatric Oncology Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      STUDY AIMS Based on prospectively collected information on ear temperatures, ANC values,&#xD;
      emergency calls and consultations for fever, and on hospitalizations for FN in children and&#xD;
      adolescents with cancer&#xD;
&#xD;
        -  to describe the frequency of episodes of FN, and of other clinically relevant FN-related&#xD;
           measures&#xD;
&#xD;
        -  to compare these frequencies and measures in reality vs. applying Bernese standard&#xD;
           limits for defining fever (ear temperature ≥39.0°C)&#xD;
&#xD;
        -  to compare these frequencies and measures applying the Bernese standard limit of ≥39.0°C&#xD;
           (LimitStandard) vs. a range of hypothetically lower limits defining fever (LimitLow)&#xD;
&#xD;
        -  to determine if it would be useful to perform an interventional study on the question of&#xD;
           different fever limits, powered to study both efficacy (frequency of FN) and safety (AE&#xD;
           in delayed FN diagnosis)&#xD;
&#xD;
        -  to use the platform of this prospective study to explore if the serum level of cortisol&#xD;
           is associated with adverse events in FN&#xD;
&#xD;
      HYPOTHESIS In children and adolescents with cancer, hypothetically modifying the definitions&#xD;
      of fever from ear temperature 39.0°C to lower limits would&#xD;
&#xD;
        -  increase the rate of FN episodes diagnosed during chemotherapy (primary endpoint).&#xD;
&#xD;
        -  increase the rate of other clinically important FN-related measures related to&#xD;
           chemotherapy exposure time (secondary endpoints 1,2,3) and outcome/treatment-related&#xD;
           measures during treatment of FN episodes diagnosed in reality (secondary endpoints&#xD;
           4,5,6).&#xD;
&#xD;
        -  not relevantly decrease the proportion of FN with AE (secondary endpoint 7).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Rate ratio of additional episodes of FN diagnosed (applying LimitLow vs. LimitStandard)</measure>
    <time_frame>until 2 weeks after last dose of chemotherapy (expected median, 6 months)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of episodes of fever</measure>
    <time_frame>until 2 weeks after last dose of chemotherapy (expected median, 6 months)</time_frame>
    <description>(Protocol: 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of emergency calls for fever</measure>
    <time_frame>until 2 weeks after last dose of chemotherapy (expected median, 6 months)</time_frame>
    <description>(Protocol: 2a)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate ratio of FN diagnosed earlier (applying LimitLow vs. LimitStandard)</measure>
    <time_frame>until 2 weeks after last dose of chemotherapy (expected median, 6 months)</time_frame>
    <description>(Protocol: 3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with blood cultures performed after start of antibiotics (AB) for prolonged fever</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 4a)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with delayed hospital discharge for prolonged fever</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 5) (Low risk FN episodes with first-day stepping down will be excluded from this analysis.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time point of empirical AB switch for prolonged fever during FN</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 6a)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with any adverse event</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 7a)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum level of cortisol</measure>
    <time_frame>at presentation with FN (in reality)</time_frame>
    <description>(Protocol: 8)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with switch of empirical AB for prolonged fever</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 4b)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with add-on of empirical antifungal therapy for prolonged fever</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 4c)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of emergency CBC with consultation for fever</measure>
    <time_frame>until 2 weeks after last dose of chemotherapy (expected median, 6 months)</time_frame>
    <description>(Protocol: 2b)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time point of starting empirical antifungal therapy for prolonged fever during FN</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 6b)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with bacteremia</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 7b)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of FN with serious medical complication</measure>
    <time_frame>until end of AB therapy for FN (estimated median, 4 days)</time_frame>
    <description>(Protocol: 7c)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">39</enrollment>
  <condition>Cancer in Children/Adolescents</condition>
  <condition>Fever in Neutropenia</condition>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <description>Pediatric patients with cancer, receiving standard chemotherapy, and receiving standard supportive therapy in case of fever in neutropenia (FN) (No intervention for study purposes)</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      1 mL serum, kept refrigerated until the end of study, then analyed as batch for cortisol,&#xD;
      then discarded.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pediatric patients diagnosed with cancer requiring chemotherapy, treated at the Division of&#xD;
        Pediatric Hematology/Oncology, Department of Pediatric, University of Bern / Inselspital,&#xD;
        CH-3010 Bern, Switzerland&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt;1 year and ≤17 years at time of recruitment&#xD;
&#xD;
          -  Chemotherapy treatment because of any malignancy for at least 2 months at time of&#xD;
             recruitment&#xD;
&#xD;
          -  Written informed consent from patients and/or parents for the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infants ≤1 year old (reason: differences in standard fever limit and method to measure&#xD;
             temperature)&#xD;
&#xD;
          -  Denied written informed consent from patients and/or parents for the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roland A Ammann, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Pediatric Hematology/Oncology, Department of Pediatrics, University of Bern, Bern, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Hematology/Oncology, Department of Pediatrics, University of Bern / Inselspital</name>
      <address>
        <city>Bern</city>
        <zip>CH-3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <results_reference>
    <citation>Ammann RA, Teuffel O, Agyeman P, Amport N, Leibundgut K. The influence of different fever definitions on the rate of fever in neutropenia diagnosed in children with cancer. PLoS One. 2015 Feb 11;10(2):e0117528. doi: 10.1371/journal.pone.0117528. eCollection 2015.</citation>
    <PMID>25671574</PMID>
  </results_reference>
  <results_reference>
    <citation>Wagner S, Brack EK, Stutz-Grunder E, Agyeman P, Leibundgut K, Teuffel O, Ammann RA. The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer. PLoS One. 2018 Feb 20;13(2):e0193227. doi: 10.1371/journal.pone.0193227. eCollection 2018.</citation>
    <PMID>29462193</PMID>
  </results_reference>
  <results_reference>
    <citation>Brack E, Wagner S, Stutz-Grunder E, Agyeman PKA, Ammann RA. Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370. Sci Data. 2020 May 26;7(1):156. doi: 10.1038/s41597-020-0504-9.</citation>
    <PMID>32457478</PMID>
  </results_reference>
  <results_reference>
    <citation>Lavieri L, Koenig C, Teuffel O, Agyeman P, Ammann RA. Temperatures and blood counts in pediatric patients treated with chemotherapy for cancer, NCT01683370. Sci Data. 2019 Jul 3;6(1):108. doi: 10.1038/s41597-019-0112-8.</citation>
    <PMID>31270328</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>October 29, 2020</last_update_submitted>
  <last_update_submitted_qc>October 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Swiss Pediatric Oncology Group</investigator_affiliation>
    <investigator_full_name>Dr. Roland Ammann</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neutropenia</mesh_term>
    <mesh_term>Fever</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/NCT01683370
org study id: PFND2012B
secondary id: KFS-2933-02-2012
nct id: NCT01683370
lead sponsor: 
collaborator: 
has dmc: No
STUDY AIMS Based on prospectively collected information on ear temperatures, ANC values,
      emergency calls and consultations for fever, and on hospitalizations for FN in children and
      adolescents with cancer

        -  to describe the frequency of episodes of FN, and of other clinically relevant FN-related
           measures

        -  to compare these frequencies and measures in reality vs. applying Bernese standard
           limits for defining fever (ear temperature ≥39.0°C)

        -  to compare these frequencies and measures applying the Bernese standard limit of ≥39.0°C
           (LimitStandard) vs. a range of hypothetically lower limits defining fever (LimitLow)

        -  to determine if it would be useful to perform an interventional study on the question of
           different fever limits, powered to study both efficacy (frequency of FN) and safety (AE
           in delayed FN diagnosis)

        -  to use the platform of this prospective study to explore if the serum level of cortisol
           is associated with adverse events in FN

      HYPOTHESIS In children and adolescents with cancer, hypothetically modifying the definitions
      of fever from ear temperature 39.0°C to lower limits would

        -  increase the rate of FN episodes diagnosed during chemotherapy (primary endpoint).

        -  increase the rate of other clinically important FN-related measures related to
           chemotherapy exposure time (secondary endpoints 1,2,3) and outcome/treatment-related
           measures during treatment of FN episodes diagnosed in reality (secondary endpoints
           4,5,6).

        -  not relevantly decrease the proportion of FN with AE (secondary endpoint 7).
observational model: Case-Only
time perspective: Prospective
measure: Rate ratio of additional episodes of FN diagnosed (applying LimitLow vs. LimitStandard)
time frame: until 2 weeks after last dose of chemotherapy (expected median, 6 months)
measure: Rate of episodes of fever
time frame: until 2 weeks after last dose of chemotherapy (expected median, 6 months)
description: (Protocol: 1)
measure: Rate of emergency calls for fever
time frame: until 2 weeks after last dose of chemotherapy (expected median, 6 months)
description: (Protocol: 2a)
measure: Rate ratio of FN diagnosed earlier (applying LimitLow vs. LimitStandard)
time frame: until 2 weeks after last dose of chemotherapy (expected median, 6 months)
description: (Protocol: 3)
measure: Proportion of FN with blood cultures performed after start of antibiotics (AB) for prolonged fever
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 4a)
measure: Proportion of FN with delayed hospital discharge for prolonged fever
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 5) (Low risk FN episodes with first-day stepping down will be excluded from this analysis.)
measure: Time point of empirical AB switch for prolonged fever during FN
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 6a)
measure: Proportion of FN with any adverse event
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 7a)
measure: Serum level of cortisol
time frame: at presentation with FN (in reality)
description: (Protocol: 8)
measure: Proportion of FN with switch of empirical AB for prolonged fever
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 4b)
measure: Proportion of FN with add-on of empirical antifungal therapy for prolonged fever
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 4c)
measure: Rate of emergency CBC with consultation for fever
time frame: until 2 weeks after last dose of chemotherapy (expected median, 6 months)
description: (Protocol: 2b)
measure: Time point of starting empirical antifungal therapy for prolonged fever during FN
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 6b)
measure: Proportion of FN with bacteremia
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 7b)
measure: Proportion of FN with serious medical complication
time frame: until end of AB therapy for FN (estimated median, 4 days)
description: (Protocol: 7c)
arm group label: Patients
description: Pediatric patients with cancer, receiving standard chemotherapy, and receiving standard supportive therapy in case of fever in neutropenia (FN) (No intervention for study purposes)
1 mL serum, kept refrigerated until the end of study, then analyed as batch for cortisol,
      then discarded.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: 17 Years
healthy volunteers: No
last name: Roland A Ammann, MD
role: Study Chair
affiliation: Pediatric Hematology/Oncology, Department of Pediatrics, University of Bern, Bern, Switzerland
facility: 
country: Switzerland
citation: Ammann RA, Teuffel O, Agyeman P, Amport N, Leibundgut K. The influence of different fever definitions on the rate of fever in neutropenia diagnosed in children with cancer. PLoS One. 2015 Feb 11;10(2):e0117528. doi: 10.1371/journal.pone.0117528. eCollection 2015.
PMID: 25671574
citation: Wagner S, Brack EK, Stutz-Grunder E, Agyeman P, Leibundgut K, Teuffel O, Ammann RA. The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer. PLoS One. 2018 Feb 20;13(2):e0193227. doi: 10.1371/journal.pone.0193227. eCollection 2018.
PMID: 29462193
citation: Brack E, Wagner S, Stutz-Grunder E, Agyeman PKA, Ammann RA. Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370. Sci Data. 2020 May 26;7(1):156. doi: 10.1038/s41597-020-0504-9.
PMID: 32457478
citation: Lavieri L, Koenig C, Teuffel O, Agyeman P, Ammann RA. Temperatures and blood counts in pediatric patients treated with chemotherapy for cancer, NCT01683370. Sci Data. 2019 Jul 3;6(1):108. doi: 10.1038/s41597-019-0112-8.
PMID: 31270328
responsible party type: Sponsor-Investigator
investigator affiliation: Swiss Pediatric Oncology Group
investigator full name: Dr. Roland Ammann
investigator title: Associate Professor
mesh term: Neutropenia
mesh term: Fever