<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/NCT03810352</url>
  </required_header>
  <id_info>
    <org_study_id>P00030227</org_study_id>
    <nct_id>NCT03810352</nct_id>
  </id_info>
  <brief_title>Association of Platelet Parameters With Bleeding Severity in Children With ITP</brief_title>
  <acronym>ITP-APPS</acronym>
  <official_title>Association of Platelet Parameters Identified by the Sysmex XN-1000 and Flow Cytometry With Concurrent and Subsequent Bleeding Severity in Children With Immune Thrombocytopenia (ITP): A Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sysmex America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Colorado</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with severe immune thrombocytopenia (ITP) present with similarly low platelet counts&#xD;
      but varying bleeding symptoms, making it difficult to predict the disease course and to&#xD;
      decide on an appropriate treatment plan. In a single-center study, platelet parameters&#xD;
      including the immature platelet fraction, the absolute immature platelet count , and&#xD;
      functional response markers were found to be significantly associated with patient bleeding&#xD;
      severity, independent of platelet count. This study aims to confirm and replicate these&#xD;
      findings in a multi-center patient population and to investigate the use of these parameters&#xD;
      to better predict disease severity and bleeding events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many children with severe immune thrombocytopenia (ITP) present with mild symptoms and their&#xD;
      disease spontaneously resolves within 3 to 6 months. However, a subset of pediatric ITP&#xD;
      patients experience severe bleeds and their symptoms persist for more than 6 to 12 months.&#xD;
      Both patient populations present with similarly low platelet counts, making it difficult to&#xD;
      predict the disease course and to decide on a treatment plan. The current American Society of&#xD;
      Hematology treatment guidelines advise that most cases of ITP may be managed through close&#xD;
      observation, while pharmacological interventions that may result in treatment-related&#xD;
      toxicities may be used in patients with more severe bleeding symptoms. In order to improve&#xD;
      the care and management of pediatric patients with ITP, it is necessary to develop a better&#xD;
      predictor of bleeding events and disease severity than the patient's platelet count.&#xD;
&#xD;
      In a previous single-center study, investigators studied the association of different&#xD;
      platelet parameters with patient bleeding severity. Using whole blood from patients diagnosed&#xD;
      with severe ITP, investigators measured the immature platelet fraction (IPF) and absolute&#xD;
      immature platelet count (IPC) through a hematology analyzer (Sysmex XN-1000). Investigators&#xD;
      performed functional tests on the platelets and analyzed them through flow cytometry. In this&#xD;
      study, the investigators found that the IPF and IPC is associated with patient bleeding&#xD;
      severity, independent of platelet count. It was also determined that functional activation&#xD;
      markers such as P-selectin and glycoprotein (GP) IIb-IIIa are significantly associated with&#xD;
      subsequent bleeding severity in children, independent of platelet count. The results of these&#xD;
      proposed studies in ITP patients may suggest clinically relevant uses of these assays.&#xD;
&#xD;
      To confirm these findings, this trial will repeat the previous study in a multi-center&#xD;
      patient population, including a greater number of patients with severe bleeding and low&#xD;
      platelet counts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 15, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Association of IPF with concurrent, subsequent and worst-ever bleeding in children with ITP.</measure>
    <time_frame>February 2019-August 2022</time_frame>
    <description>Evaluate in a multi-center study the association, independent of platelet count, of IPF measured by the Sysmex XN-1000 with concurrent, subsequent, and worst-ever bleeding in children with ITP.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Association of IPC with concurrent, subsequent, and worst-ever bleeding in children with ITP</measure>
    <time_frame>February 2019-August 2022</time_frame>
    <description>Evaluate in a multi-center study the association, independent of platelet count, of immature platelet parameters measured by the Sysmex XN-1000 (IPC, Plt-F, and FSC and other research parameters as applicable) with concurrent, subsequent, and worst-ever bleeding in children with ITP.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Association of platelet function markers with concurrent, subsequent, and worst-ever bleeding in children with ITP.</measure>
    <time_frame>February 2019-August 2022</time_frame>
    <description>Evaluate in a multi-center study the association, independent of platelet count, off circulating andd agonist-stimulated platelet surface P-selectin and activated GPIIb-IIIa with concurrent, subsequent, and worst-ever bleeding in children with ITP.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Immune Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Patients with ITP</arm_group_label>
    <description>Patients with primary or secondary immune thrombocytopenia</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The investigators are using blood samples to measure platelet parameters and biomarkers for&#xD;
      platelet function.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pediatric patients diagnosed with primary or secondary immune thrombocytopenia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with primary or secondary immune thrombocytopenia.&#xD;
&#xD;
          -  Platelet count of &lt; 50 x 10^9/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  May not have received aspirin 10 days prior to study entry.&#xD;
&#xD;
          -  May not have received nonsteroidal anti-inflammatory drugs (NSAIDs) 3 days prior to&#xD;
             study entry.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>20 Years</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Andrew L. Frelinger, PhD</last_name>
    <phone>617-919-2537</phone>
    <email>andrew.frelinger@childrens.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Micaela Hayton</last_name>
    <phone>617-355-3748</phone>
    <email>Micaela.Hayton@childrens.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Taizo Nakano, MD</last_name>
      <phone>720-777-6740</phone>
      <email>Taizo.Nakano@childrenscolorado.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Timothy Mercier</last_name>
      <phone>617-355-7203</phone>
      <email>Timothy.Mercier@childrens.harvard.edu</email>
    </contact>
    <contact_backup>
      <last_name>Julia MW Wong, PHD RD</last_name>
      <phone>617-355-7407</phone>
      <email>julia.wong@childrens.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Andrew L. Frelinger, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rachael Grace, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Cindy Neunert, MD, MSCS</last_name>
      <phone>212-342-3853</phone>
      <email>cn2401@cumc.columbia.edu</email>
    </contact>
  </location>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Rothman, MD</last_name>
      <phone>919-684-3401</phone>
      <email>jennifer.rothman@duke.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele Lambert, MD, MTR</last_name>
      <phone>215-590-4667</phone>
      <email>LAMBERTM@email.chop.edu</email>
    </contact>
    <contact_backup>
      <last_name>Abinaya Arulselvan</last_name>
      <phone>215-590-3582</phone>
      <email>arulselvaa@email.chop.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Taylor Kim, MD</last_name>
      <phone>832-822-4242</phone>
      <email>teolmste@texaschildrens.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Andrew Frelinger</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>ITP</keyword>
  <keyword>platelet function</keyword>
  <keyword>Sysmex</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic, Idiopathic</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/NCT03810352
org study id: P00030227
nct id: NCT03810352
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with severe immune thrombocytopenia (ITP) present with similarly low platelet counts
      but varying bleeding symptoms, making it difficult to predict the disease course and to
      decide on an appropriate treatment plan. In a single-center study, platelet parameters
      including the immature platelet fraction, the absolute immature platelet count , and
      functional response markers were found to be significantly associated with patient bleeding
      severity, independent of platelet count. This study aims to confirm and replicate these
      findings in a multi-center patient population and to investigate the use of these parameters
      to better predict disease severity and bleeding events.
Many children with severe immune thrombocytopenia (ITP) present with mild symptoms and their
      disease spontaneously resolves within 3 to 6 months. However, a subset of pediatric ITP
      patients experience severe bleeds and their symptoms persist for more than 6 to 12 months.
      Both patient populations present with similarly low platelet counts, making it difficult to
      predict the disease course and to decide on a treatment plan. The current American Society of
      Hematology treatment guidelines advise that most cases of ITP may be managed through close
      observation, while pharmacological interventions that may result in treatment-related
      toxicities may be used in patients with more severe bleeding symptoms. In order to improve
      the care and management of pediatric patients with ITP, it is necessary to develop a better
      predictor of bleeding events and disease severity than the patient's platelet count.

      In a previous single-center study, investigators studied the association of different
      platelet parameters with patient bleeding severity. Using whole blood from patients diagnosed
      with severe ITP, investigators measured the immature platelet fraction (IPF) and absolute
      immature platelet count (IPC) through a hematology analyzer (Sysmex XN-1000). Investigators
      performed functional tests on the platelets and analyzed them through flow cytometry. In this
      study, the investigators found that the IPF and IPC is associated with patient bleeding
      severity, independent of platelet count. It was also determined that functional activation
      markers such as P-selectin and glycoprotein (GP) IIb-IIIa are significantly associated with
      subsequent bleeding severity in children, independent of platelet count. The results of these
      proposed studies in ITP patients may suggest clinically relevant uses of these assays.

      To confirm these findings, this trial will repeat the previous study in a multi-center
      patient population, including a greater number of patients with severe bleeding and low
      platelet counts.
observational model: Cohort
time perspective: Cross-Sectional
measure: Association of IPF with concurrent, subsequent and worst-ever bleeding in children with ITP.
time frame: February 2019-August 2022
description: Evaluate in a multi-center study the association, independent of platelet count, of IPF measured by the Sysmex XN-1000 with concurrent, subsequent, and worst-ever bleeding in children with ITP.
measure: Association of IPC with concurrent, subsequent, and worst-ever bleeding in children with ITP
time frame: February 2019-August 2022
description: Evaluate in a multi-center study the association, independent of platelet count, of immature platelet parameters measured by the Sysmex XN-1000 (IPC, Plt-F, and FSC and other research parameters as applicable) with concurrent, subsequent, and worst-ever bleeding in children with ITP.
measure: Association of platelet function markers with concurrent, subsequent, and worst-ever bleeding in children with ITP.
time frame: February 2019-August 2022
description: Evaluate in a multi-center study the association, independent of platelet count, off circulating andd agonist-stimulated platelet surface P-selectin and activated GPIIb-IIIa with concurrent, subsequent, and worst-ever bleeding in children with ITP.
arm group label: Patients with ITP
description: Patients with primary or secondary immune thrombocytopenia
The investigators are using blood samples to measure platelet parameters and biomarkers for
      platelet function.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Months
maximum age: 20 Years
last name: Andrew L. Frelinger, PhD
phone: 617-919-2537
email: andrew.frelinger@childrens.harvard.edu
last name: Micaela Hayton
phone: 617-355-3748
email: Micaela.Hayton@childrens.harvard.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Andrew Frelinger
investigator title: Assistant Professor of Pediatrics, Harvard Medical School
mesh term: Thrombocytopenia
mesh term: Purpura, Thrombocytopenic, Idiopathic