<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/NCT03828279</url>
  </required_header>
  <id_info>
    <org_study_id>HAERegistry</org_study_id>
    <nct_id>NCT03828279</nct_id>
  </id_info>
  <brief_title>Global Registry to Gather Data on Natural History of Patients With Hereditary Angioedema Type I and II</brief_title>
  <acronym>HGR</acronym>
  <official_title>The Global Registry on Hereditary Angioedema Type I and II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HAE Global Registry Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>HAE Global Registry Foundation</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The objective of this international hereditary angioedema (HAE) register is to collect&#xD;
      homogeneous clinical and laboratory data on patients with HAE type I and II gathering better&#xD;
      information on the natural course of the disease and detecting therapeutic options to manage&#xD;
      it.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is an international multicenter disease registry, the principal investigator at each&#xD;
      center is responsible for competent ethic committee/institutional review board approval and&#xD;
      for identifying co-investigators, who collect patients' informed consent and insert patients'&#xD;
      data. Participating patients own their data. Upon acceptance of the informed consent, the&#xD;
      treating physician transfers data of the case report form (CRF) to a specifically designed&#xD;
      electronic support (eCRF) and the patients enter data on attacks. Physicians at center&#xD;
      fill-in the eCRF with data for demography, diagnosis, prophylaxis and associated diseases.&#xD;
      Plasma levels of C1 inhibitor antigen and function and of C4 antigen document laboratory&#xD;
      diagnostic criteria. Each patient has a national identifier code. Patients fill-in attack&#xD;
      reports that encompass duration, severity and treatment of each angioedema episode. C1&#xD;
      inhibitor coding gene (SERPING1) genotype is entered according to the last Hugo nomenclature.&#xD;
      Yearly update of information is recommended, patients with follow up above two years are&#xD;
      moved in a separate area and excluded from analysis. Each patient prospectively fills data on&#xD;
      attacks. On a specific informed consent, the patient can agree on storing biological material&#xD;
      (plasma and nucleic acids) for research purposes.&#xD;
&#xD;
      The data processor is an innovative start-up (Cloud-R s.r.l. Milan, Italy) that manages all&#xD;
      data according to a specific contract and in compliance with current regulation on sensitive&#xD;
      data security and processing. The Registry, delivered in the mode of Registry-as-a-Service&#xD;
      (RaaS), is designed following General Data Protection Regulation (GDPR) guidelines, and&#xD;
      issues regular software and infrastructure enhancements as a part of the normal operational&#xD;
      mode. The system generates statistics of aggregated anonymized data following the&#xD;
      participating centers' hierarchy levels and Global Registry governance rules. Patients supply&#xD;
      data on attacks either on paper support or using a Web form or a mobile application. These&#xD;
      data will flow into a staging area for physician validation before being considered valid for&#xD;
      statistics. For each entry the system updates in real-time all the statistics and dashboards.&#xD;
      The platform has configurable functionalities to support data quality management. It provides&#xD;
      data format validation, integration to external qualified libraries, alerts, dashboards,&#xD;
      automatic index calculations, advanced filters and queries, data change log. This open&#xD;
      architecture, allows integration of the system, via standard API's, to external or&#xD;
      sub-registries, registries, biobanks and clinical bioinformatics tools, i.e. for specific&#xD;
      trial studies leveraging a specific cluster of patients already present in the Global&#xD;
      Registry.&#xD;
&#xD;
      An independent non-profit foundation (HGRF) made of representatives of patients' associations&#xD;
      is in charge for funding and delegates all the management to the HAE Global Registry Board&#xD;
      (HGRB). The HGRB is in charge for operational, assisted by the HAE Global Registry Scientific&#xD;
      Committee (HGRSC) for topics of competence. No registry member, center, group or board can&#xD;
      access the entire set of data. All registry members, as single or group, can propose studies&#xD;
      based on aggregated data by addressing the request to the HGRSC. Analysis and studies of data&#xD;
      at local centers can occur at any time. Members of HGRB and HGRSC are elected to be&#xD;
      representative of different cultural and geographic backgrounds. Their offices have a&#xD;
      two-year term with no more than one consecutive renewal. Angioedema centers can join the&#xD;
      Registry upon request to the HGRB . The registry quality control system periodically checks&#xD;
      Registry entries and compliance of eCRF with the source data. For each information, the&#xD;
      system will grant traceability of time and author.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</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>1 Year</target_duration>
  <primary_outcome>
    <measure>Number of angioedema events</measure>
    <time_frame>Through study completion, an average of 5 years</time_frame>
    <description>Number of angioedema events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of angioedema events</measure>
    <time_frame>Through study completion, an average of 5 years</time_frame>
    <description>Time in hours of presence of angioedema symptoms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of angioedema events</measure>
    <time_frame>through study completion, an average of 5 years</time_frame>
    <description>Number of severe, moderate, mild angioedema symptoms based on a three point scale patient reported outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comorbidities</measure>
    <time_frame>Through study completion , an average of 5 years</time_frame>
    <description>Number and type of comorbidities recorded according to the International Classification of Diseases 9 codes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-Emergent comorbidities</measure>
    <time_frame>Through study completion , an average of 5 years</time_frame>
    <description>Incidence of comorbidities emerging in patients exposed to specific treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment efficacy</measure>
    <time_frame>Through study completion , an average of 5 years</time_frame>
    <description>Hours of presence of angioedema symptoms during specific long term prophylaxis</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">220</enrollment>
  <condition>Hereditary Angioedema Type I and II</condition>
  <arm_group>
    <arm_group_label>hereditary angioedema type I</arm_group_label>
    <description>Patients were diagnosed as C1 inhibitor HAE type I when functional and antigenic C1 inhibitor were ≤ 50% of normal</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hereditary angioedema type II</arm_group_label>
    <description>Patients were diagnosed as type II when functional C1 inhibitor was ≤50% and antigenic was &gt;50% of normal</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>functional and antigenic C1 inhibitor</intervention_name>
    <description>Diagnosis of HAE is based on personal and/or family history of angioedema and on C1 inhibitor functional or antigenic plasma levels ≤50% of normal.</description>
    <arm_group_label>hereditary angioedema type I</arm_group_label>
    <arm_group_label>hereditary angioedema type II</arm_group_label>
    <other_name>genetic analysis</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Sodium Citrate samples are collected form patients for testing plasma levels of C1 inhibitor&#xD;
      antigen and function and C4 antigen. Cells are collected for DNA extraction and detection of&#xD;
      mutations in SERPING1&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients diagnosed with HAE type I and II and followed by a referral center for angioedema&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients diagnosed with HAE type I and II with signed informed consent&#xD;
&#xD;
          -  laboratory diagnostic criteria documenting plasma levels of C1 inhibitor antigen and&#xD;
             function and of C4 antigen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients without HAE type I and II&#xD;
&#xD;
          -  patients without documented laboratory diagnostic criteria&#xD;
&#xD;
          -  patients not capable to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>marco cicardi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HAE Global Registry Foundation</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>marco cicardi, MD</last_name>
    <phone>+39 0239042516</phone>
    <email>marco.cicardi@unimi.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>ASST FBF Sacco</name>
      <address>
        <city>Milan</city>
        <zip>20157</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>marco cicardi, M.D.</last_name>
      <phone>+3950319829</phone>
      <email>marco.cicardi@unimi.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>February 3, 2019</last_update_submitted>
  <last_update_submitted_qc>February 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>angioedema</keyword>
  <keyword>disease registry</keyword>
  <keyword>C1 inhibitor</keyword>
  <keyword>anti bradykinin treatments</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angioedema</mesh_term>
    <mesh_term>Angioedemas, Hereditary</mesh_term>
    <mesh_term>Hereditary Angioedema Types I and II</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Complement C1 Inhibitor Protein</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All registry members, as single or group, can propose studies based on aggregated anonymized data by addressing the request to the HAE Global Registry Scientific Committee (HGRSC)</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>entire study period</ipd_time_frame>
    <ipd_access_criteria>to be a member of the HAERegistry and have the approval of the HGRSC to analyze data</ipd_access_criteria>
  </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/NCT03828279
org study id: HAERegistry
nct id: NCT03828279
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this international hereditary angioedema (HAE) register is to collect
      homogeneous clinical and laboratory data on patients with HAE type I and II gathering better
      information on the natural course of the disease and detecting therapeutic options to manage
      it.
It is an international multicenter disease registry, the principal investigator at each
      center is responsible for competent ethic committee/institutional review board approval and
      for identifying co-investigators, who collect patients' informed consent and insert patients'
      data. Participating patients own their data. Upon acceptance of the informed consent, the
      treating physician transfers data of the case report form (CRF) to a specifically designed
      electronic support (eCRF) and the patients enter data on attacks. Physicians at center
      fill-in the eCRF with data for demography, diagnosis, prophylaxis and associated diseases.
      Plasma levels of C1 inhibitor antigen and function and of C4 antigen document laboratory
      diagnostic criteria. Each patient has a national identifier code. Patients fill-in attack
      reports that encompass duration, severity and treatment of each angioedema episode. C1
      inhibitor coding gene (SERPING1) genotype is entered according to the last Hugo nomenclature.
      Yearly update of information is recommended, patients with follow up above two years are
      moved in a separate area and excluded from analysis. Each patient prospectively fills data on
      attacks. On a specific informed consent, the patient can agree on storing biological material
      (plasma and nucleic acids) for research purposes.

      The data processor is an innovative start-up (Cloud-R s.r.l. Milan, Italy) that manages all
      data according to a specific contract and in compliance with current regulation on sensitive
      data security and processing. The Registry, delivered in the mode of Registry-as-a-Service
      (RaaS), is designed following General Data Protection Regulation (GDPR) guidelines, and
      issues regular software and infrastructure enhancements as a part of the normal operational
      mode. The system generates statistics of aggregated anonymized data following the
      participating centers' hierarchy levels and Global Registry governance rules. Patients supply
      data on attacks either on paper support or using a Web form or a mobile application. These
      data will flow into a staging area for physician validation before being considered valid for
      statistics. For each entry the system updates in real-time all the statistics and dashboards.
      The platform has configurable functionalities to support data quality management. It provides
      data format validation, integration to external qualified libraries, alerts, dashboards,
      automatic index calculations, advanced filters and queries, data change log. This open
      architecture, allows integration of the system, via standard API's, to external or
      sub-registries, registries, biobanks and clinical bioinformatics tools, i.e. for specific
      trial studies leveraging a specific cluster of patients already present in the Global
      Registry.

      An independent non-profit foundation (HGRF) made of representatives of patients' associations
      is in charge for funding and delegates all the management to the HAE Global Registry Board
      (HGRB). The HGRB is in charge for operational, assisted by the HAE Global Registry Scientific
      Committee (HGRSC) for topics of competence. No registry member, center, group or board can
      access the entire set of data. All registry members, as single or group, can propose studies
      based on aggregated data by addressing the request to the HGRSC. Analysis and studies of data
      at local centers can occur at any time. Members of HGRB and HGRSC are elected to be
      representative of different cultural and geographic backgrounds. Their offices have a
      two-year term with no more than one consecutive renewal. Angioedema centers can join the
      Registry upon request to the HGRB . The registry quality control system periodically checks
      Registry entries and compliance of eCRF with the source data. For each information, the
      system will grant traceability of time and author.
observational model: Cohort
time perspective: Prospective
measure: Number of angioedema events
time frame: Through study completion, an average of 5 years
description: Number of angioedema events
measure: Time of angioedema events
time frame: Through study completion, an average of 5 years
description: Time in hours of presence of angioedema symptoms
measure: Severity of angioedema events
time frame: through study completion, an average of 5 years
description: Number of severe, moderate, mild angioedema symptoms based on a three point scale patient reported outcome
measure: Comorbidities
time frame: Through study completion , an average of 5 years
description: Number and type of comorbidities recorded according to the International Classification of Diseases 9 codes
measure: Treatment-Emergent comorbidities
time frame: Through study completion , an average of 5 years
description: Incidence of comorbidities emerging in patients exposed to specific treatments
measure: Treatment efficacy
time frame: Through study completion , an average of 5 years
description: Hours of presence of angioedema symptoms during specific long term prophylaxis
arm group label: hereditary angioedema type I
description: Patients were diagnosed as C1 inhibitor HAE type I when functional and antigenic C1 inhibitor were ≤ 50% of normal
arm group label: hereditary angioedema type II
description: Patients were diagnosed as type II when functional C1 inhibitor was ≤50% and antigenic was >50% of normal
intervention type: Diagnostic Test
intervention name: functional and antigenic C1 inhibitor
description: Diagnosis of HAE is based on personal and/or family history of angioedema and on C1 inhibitor functional or antigenic plasma levels ≤50% of normal.
arm group label: hereditary angioedema type I
arm group label: hereditary angioedema type II
other name: genetic analysis
Sodium Citrate samples are collected form patients for testing plasma levels of C1 inhibitor
      antigen and function and C4 antigen. Cells are collected for DNA extraction and detection of
      mutations in SERPING1
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: marco cicardi, MD
role: Principal Investigator
affiliation: HAE Global Registry Foundation
last name: marco cicardi, MD
phone: +39 0239042516
email: marco.cicardi@unimi.it
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Angioedema
mesh term: Angioedemas, Hereditary
mesh term: Hereditary Angioedema Types I and II
mesh term: Complement C1 Inhibitor Protein
sharing ipd: Yes
ipd description: All registry members, as single or group, can propose studies based on aggregated anonymized data by addressing the request to the HAE Global Registry Scientific Committee (HGRSC)
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: entire study period
ipd access criteria: to be a member of the HAERegistry and have the approval of the HGRSC to analyze data