<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/NCT03815357</url>
  </required_header>
  <id_info>
    <org_study_id>35266C</org_study_id>
    <nct_id>NCT03815357</nct_id>
  </id_info>
  <brief_title>What is the Incidence of an Immune Disorder in Children With Invasive Pneumococcal Disease (IPD)?</brief_title>
  <official_title>What is the Incidence of an Immune Disorder in Children With Invasive Pneumococcal Disease (IPD)? A Prospective Cohort Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Murdoch Childrens Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Royal Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Murdoch Childrens Research Institute</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>
      This is a multicentre prospective audit to determine the incidence of immunodeficiency in&#xD;
      children with IPD.&#xD;
&#xD;
      Aims and/or research question of the project&#xD;
&#xD;
        1. To determine the incidence of primary immunodeficiency in children &gt;2 years who present&#xD;
           with IPD&#xD;
&#xD;
        2. To determine the types of immunodeficiency associated with IPD in children&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</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>incidence of primary immunodeficiency in children who present with invasive pneumococcal disease</measure>
    <time_frame>3 years</time_frame>
    <description>This will be picked up upon prospective immunological testing, after identification of patients with invasive pneumococcal disease. A series of tests will be performed depending on the clinical opinion of the immunology team. Such tests may include lymphocyte subsets, complement function, serum immunoglobulin levels, memory B cells, vaccine antibody responses, etc.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>types of immunodeficiency associated with children who present with invasive pneumococcal disease</measure>
    <time_frame>3 years</time_frame>
    <description>This will be determined based on the testing performed by the immunologists.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>whether increased referrals of children who present with invasive pneumococcal disease for investigation of primary immunodeficiency facilitates early detection</measure>
    <time_frame>3 years</time_frame>
    <description>This information will come from reviewing the case series of patients who are identified from this study. The incidence of those with primary immunodeficiency will be analysed against known background rates of diagnoses.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">380</enrollment>
  <condition>Invasive Pneumococcal Disease, Recurrent Isolated, 1</condition>
  <condition>Invasive Pneumococcal Disease, Recurrent Isolated, 2</condition>
  <condition>Invasive Pneumococcal Disease, Protection Against</condition>
  <condition>Primary Immunodeficiency</condition>
  <arm_group>
    <arm_group_label>Children with IPD</arm_group_label>
    <description>Children with IPD will be referred for immunological evaluation. The protocol for immune work up will be the same but between centres there is variation in the age criteria for referral i.e. &gt;2 years in some, &gt;6 months in others.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Referral to Immunology</intervention_name>
    <description>Screening for primary immunodeficiency including splenic dysfunction</description>
    <arm_group_label>Children with IPD</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Children presenting with invasive pneumococcal disease at any of the participating sites&#xD;
        listed.&#xD;
&#xD;
        Invasive pneumococcal disease is defined by isolation by culture or PCR of Streptococcus&#xD;
        pneumoniae from sterile sites including blood, cerebrospinal fluid (CSF), joint fluid or&#xD;
        pleural fluid. In those patients with bacteraemia, their presentation needs to be&#xD;
        accompanied by signs of sepsis.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children aged 0 to 18 years admitted to one of the six centres with IPD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children who do not fulfil the age criteria for immunological evaluation at that&#xD;
             particular site e.g. aged &lt;2 years at Royal Children's Hospital.&#xD;
&#xD;
          -  Children with a known underlying condition predisposing to IPD i.e. nephrotic&#xD;
             syndrome.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sydney Children's Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adelaide Women's and Children's Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Health</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Children's Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3049</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lady Cilento Children's Hospital</name>
      <address>
        <city>Brisbane</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital and Coast District Health Board</name>
      <address>
        <city>Wellington</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
  </location_countries>
  <reference>
    <citation>Gaschignard J, Levy C, Chrabieh M, Boisson B, Bost-Bru C, Dauger S, Dubos F, Durand P, Gaudelus J, Gendrel D, Gras Le Guen C, Grimprel E, Guyon G, Jeudy C, Jeziorski E, Leclerc F, Leger PL, Lesage F, Lorrot M, Pellier I, Pinquier D, de Pontual L, Sachs P, Thomas C, Tissieres P, Valla FV, Desprez P, Fremeaux-Bacchi V, Varon E, Bossuyt X, Cohen R, Abel L, Casanova JL, Puel A, Picard C. Invasive pneumococcal disease in children can reveal a primary immunodeficiency. Clin Infect Dis. 2014 Jul 15;59(2):244-51. doi: 10.1093/cid/ciu274. Epub 2014 Apr 23.</citation>
    <PMID>24759830</PMID>
  </reference>
  <reference>
    <citation>Picard C, Puel A, Bustamante J, Ku CL, Casanova JL. Primary immunodeficiencies associated with pneumococcal disease. Curr Opin Allergy Clin Immunol. 2003 Dec;3(6):451-9. doi: 10.1097/00130832-200312000-00006.</citation>
    <PMID>14612669</PMID>
  </reference>
  <reference>
    <citation>Alsina L, Basteiro MG, de Paz HD, Inigo M, de Sevilla MF, Trivino M, Juan M, Munoz-Almagro C. Recurrent invasive pneumococcal disease in children: underlying clinical conditions, and immunological and microbiological characteristics. PLoS One. 2015 Mar 4;10(3):e0118848. doi: 10.1371/journal.pone.0118848. eCollection 2015.</citation>
    <PMID>25738983</PMID>
  </reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>January 20, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>June 30, 2022</last_update_submitted>
  <last_update_submitted_qc>June 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>streptococcus pneumoniae</keyword>
  <keyword>invasive pneumococcal disease</keyword>
  <keyword>primary immunodeficiency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumococcal Infections</mesh_term>
    <mesh_term>Primary Immunodeficiency Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
    <mesh_term>Immune System Diseases</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_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/NCT03815357
org study id: 35266C
nct id: NCT03815357
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicentre prospective audit to determine the incidence of immunodeficiency in
      children with IPD.

      Aims and/or research question of the project

        1. To determine the incidence of primary immunodeficiency in children >2 years who present
           with IPD

        2. To determine the types of immunodeficiency associated with IPD in children
observational model: Cohort
time perspective: Prospective
measure: incidence of primary immunodeficiency in children who present with invasive pneumococcal disease
time frame: 3 years
description: This will be picked up upon prospective immunological testing, after identification of patients with invasive pneumococcal disease. A series of tests will be performed depending on the clinical opinion of the immunology team. Such tests may include lymphocyte subsets, complement function, serum immunoglobulin levels, memory B cells, vaccine antibody responses, etc.
measure: types of immunodeficiency associated with children who present with invasive pneumococcal disease
time frame: 3 years
description: This will be determined based on the testing performed by the immunologists.
measure: whether increased referrals of children who present with invasive pneumococcal disease for investigation of primary immunodeficiency facilitates early detection
time frame: 3 years
description: This information will come from reviewing the case series of patients who are identified from this study. The incidence of those with primary immunodeficiency will be analysed against known background rates of diagnoses.
arm group label: Children with IPD
description: Children with IPD will be referred for immunological evaluation. The protocol for immune work up will be the same but between centres there is variation in the age criteria for referral i.e. >2 years in some, >6 months in others.
intervention type: Other
intervention name: Referral to Immunology
description: Screening for primary immunodeficiency including splenic dysfunction
arm group label: Children with IPD
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 0 Months
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: New Zealand
citation: Gaschignard J, Levy C, Chrabieh M, Boisson B, Bost-Bru C, Dauger S, Dubos F, Durand P, Gaudelus J, Gendrel D, Gras Le Guen C, Grimprel E, Guyon G, Jeudy C, Jeziorski E, Leclerc F, Leger PL, Lesage F, Lorrot M, Pellier I, Pinquier D, de Pontual L, Sachs P, Thomas C, Tissieres P, Valla FV, Desprez P, Fremeaux-Bacchi V, Varon E, Bossuyt X, Cohen R, Abel L, Casanova JL, Puel A, Picard C. Invasive pneumococcal disease in children can reveal a primary immunodeficiency. Clin Infect Dis. 2014 Jul 15;59(2):244-51. doi: 10.1093/cid/ciu274. Epub 2014 Apr 23.
PMID: 24759830
citation: Picard C, Puel A, Bustamante J, Ku CL, Casanova JL. Primary immunodeficiencies associated with pneumococcal disease. Curr Opin Allergy Clin Immunol. 2003 Dec;3(6):451-9. doi: 10.1097/00130832-200312000-00006.
PMID: 14612669
citation: Alsina L, Basteiro MG, de Paz HD, Inigo M, de Sevilla MF, Trivino M, Juan M, Munoz-Almagro C. Recurrent invasive pneumococcal disease in children: underlying clinical conditions, and immunological and microbiological characteristics. PLoS One. 2015 Mar 4;10(3):e0118848. doi: 10.1371/journal.pone.0118848. eCollection 2015.
PMID: 25738983
responsible party type: Sponsor
mesh term: Pneumococcal Infections
mesh term: Primary Immunodeficiency Diseases
mesh term: Immunologic Deficiency Syndromes
mesh term: Immune System Diseases
mesh term: Recurrence
sharing ipd: No