<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/NCT02979119</url>
  </required_header>
  <id_info>
    <org_study_id>Version 6.0 May 2020</org_study_id>
    <nct_id>NCT02979119</nct_id>
  </id_info>
  <brief_title>The European Paediatric Network for Haemophilia Management ( PedNet Registry)</brief_title>
  <acronym>PedNet</acronym>
  <official_title>The European Paediatric Network for Haemophilia Management and the PedNet Haemophilia Registry</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PedNet Haemophilia Research Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lund University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>PedNet Haemophilia Research Foundation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale:&#xD;
&#xD;
      Haemophilia is a rare disease; to improve knowledge international collaboration is needed.&#xD;
      Well-defined clinical data will be collected from complete cohorts in order to prevent&#xD;
      selection bias.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To collect data on bleeding during neonatal period, endogenous (genetic) and exogenous&#xD;
      (treatment-related) determinants of inhibitor development and long term outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design: Multicenter Prospective Observational Birth Cohort Study&#xD;
&#xD;
      Population:&#xD;
&#xD;
      Patients with haemophilia A and B with FVIII/IX levels of &lt;1 to 25% born between 1-1-2000 and&#xD;
      1-1-2030.&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      No intervention; only documentation of patient characteristics and parameters of routine&#xD;
      patient care and outcome&#xD;
&#xD;
      Main outcome parameters:&#xD;
&#xD;
      Outcome: clinically relevant inhibitor development, bleeding pattern and joint status on&#xD;
      physical examination and imaging.&#xD;
&#xD;
      Determinants: baseline FVIII/IX levels, measurement of inhibitory antibodies, family history,&#xD;
      FVIII/IX gene mutation, details on replacement therapy (according to each infusion for the&#xD;
      first 50 treatment days, and annually thereafter) and surgeries.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness:&#xD;
&#xD;
        -  No burden for the patients. Well-defined clinical data will be collected from the&#xD;
           medical files. Participating in this registry will not change the number of visits to&#xD;
           the clinic. All outcome parameters that are collected (including laboratory results) are&#xD;
           part of routine clinical care.&#xD;
&#xD;
        -  Direct benefit is not to be expected. However, the direct interaction between centres&#xD;
           that treat patients with rare diseases improves both clinical care and will result in&#xD;
           better guidelines and as such may provide indirect benefit.&#xD;
&#xD;
        -  Multicentre participation: haemophilia is a very rare condition. Therefore, collecting&#xD;
           data on a multi-centre observational cohort is the only way to study this specific&#xD;
           population.&#xD;
&#xD;
        -  The registry concerns young boys with haemophilia and cannot be performed in older&#xD;
           patients, as &gt;90% of inhibitors occur develop during the first 50 exposure days, and the&#xD;
           results of prophylactic replacement therapy are highly dependent on the initiation of&#xD;
           this treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2029</completion_date>
  <primary_completion_date type="Anticipated">December 2029</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>20 Years</target_duration>
  <primary_outcome>
    <measure>Number of patients with antibody development to exogenous clotting factors</measure>
    <time_frame>Until patient reaches age of 18</time_frame>
    <description>Allo-antibodies against Fact VIII and IX; Blood test: measurement in Bethesda units (BU), positive according to local standards, for most labs &gt;0.5 BU</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Long term outcome of haemophilia on joint status using the Hemophilia Joint Health Score (HJHS) and MRI techniques.</measure>
    <time_frame>From diagnose every 5 years until patient reaches age of 18</time_frame>
    <description>Effect of different prophylactic regimen on bleedings and joint damage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long term outcome different Immune Tolerance Induction (ITI) therapies in patients with inhibitor.</measure>
    <time_frame>From date first positive inhibitor titer every 3 years until patient reaches age of 18</time_frame>
    <description>Effect of different ITI therapies on bleeding and joint damage. Joint damage is assessed using the HJHS and MRI.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">4000</enrollment>
  <condition>Factor VIII Deficiency</condition>
  <condition>Factor IX Deficiency</condition>
  <arm_group>
    <arm_group_label>Cohort I</arm_group_label>
    <description>Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX &lt;1%) haemophilia A or B, born from January 1st 2000 until January 1st 2009 who have been or are to be treated with coagulation proteins in one of the participating centres</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort II</arm_group_label>
    <description>Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX &lt;1%) haemophilia A or B, born from January 1st 2009 until January 1st 2020 who have been or are to be treated with coagulation proteins in one of the participating centres</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort III</arm_group_label>
    <description>Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX &lt;1%) haemophilia A or B, born from January 1st 2020 until January 1st 2030 who have been or are to be treated with coagulation proteins in one of the participating centres</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX&#xD;
        &lt;1%) haemophilia A or B, born from January 1st 2000 until January 1st 2030 who have been or&#xD;
        are to be treated in one of the participating centres&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with Haemophilia A or B&#xD;
&#xD;
          -  Factor VIII/ IX activity of &lt;1 to 25%&#xD;
&#xD;
          -  Complete records of Factor treatment and bleeds&#xD;
&#xD;
          -  Treated in one of the participating centres&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients referred because of an inhibitor*&#xD;
&#xD;
          -  Informed consent not obtained&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rolf Ljung, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lund University Hospital, Malmo, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>H. Marijke Van den Berg, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Medical Center Utrecht, The Netherlands</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>H. Marijke van den Berg, MD, PhD</last_name>
    <phone>+31850299993</phone>
    <email>h.marijke.vandenberg@pednet.eu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ella van Hardeveld, MANP</last_name>
    <phone>+31850299993</phone>
    <email>e.m.vanhardeveld@pednet.eu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Universitäts-Klinik für Kinder- und Jugendheilkunde</name>
      <address>
        <city>Graz</city>
        <zip>A-8036</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Medical University of Vienna - Department of Paediatrics</name>
      <address>
        <city>Vienna</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christoph Male, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Service of Pediatric Haematology University Hospital Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>B-3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christel Van Geet, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Division of Hematology/Oncology Hôpital St Justine</name>
      <address>
        <city>Montréal</city>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>George Rivard, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Division of Haematology/Oncology Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <zip>M5G-1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuel Carcao, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Haemophilia Comprehensive Care Centre, Centre for Thrombosis and Haemostasis Children's University Hospital Brno</name>
      <address>
        <city>Brno</city>
        <zip>613 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jan Blatny, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Department of Paediatric Haematology/oncology - University Hospital Motol</name>
      <address>
        <city>Praha</city>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Esther Zapotocka, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Department of Pediatrics Århus Kommunehospital Skejby Sygehus</name>
      <address>
        <city>Aarhus</city>
        <zip>DK-8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Torben Stamm Mikkelsen, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Helsinki University Hospital</name>
      <address>
        <city>Helsinki</city>
        <zip>FIN-00029</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Minna Koskenvuo, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Service Hématologique Centre Regional Traitement d'Hemophilie Bicetre</name>
      <address>
        <city>Le Kremlin Bicêtre</city>
        <zip>F-94270</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roseline d'Oiron, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Service d'Hématologie Pédiatrique Hôpital Universitaire La Timone</name>
      <address>
        <city>Marseille Cedex-05</city>
        <zip>F-13385</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hervé Chambost, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre de traitement des hémophiles Hôpital Universitaire Purpan</name>
      <address>
        <city>Toulouse</city>
        <zip>F-31052</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ségolène Claeyssens, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut für Experimentelle Hämatologie und Transfusionsmedizin Universitätsklinikum Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>D-53127</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Johannes Oldenburg, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Klinik Bremen-Mitte Prof.-Hess-Kinderklinik</name>
      <address>
        <city>Bremen</city>
        <zip>D 28177</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martina Bührlen, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital Frankfurt &amp; Goethe University - Clinical and Molecular Hemostasis, Department of Pediatrics</name>
      <address>
        <city>Frankfurt am Main</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christoph Königs, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. v. Haunersches Kinderspital University of Munich</name>
      <address>
        <city>Munich</city>
        <zip>D-80337</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karin Kurnik, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hämophilie Zentrum Rhein Main</name>
      <address>
        <city>Mörfelden-Walldorf</city>
        <zip>D-64546</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carmen Escuriola, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Haemophilia-Haemostasis Unit St. Sophia Children's Hospital</name>
      <address>
        <city>Athens</city>
        <zip>GR-11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helen Pergantou, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dept of Paediatric Haematology Our Lady's Children's Hospital for Sick Children Crumlin</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beatrice Nolan, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The National Hemophilia Center Sheba Medical Center, Tel Hashomer</name>
      <address>
        <city>Ramat Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gili Kenet, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gaslini Hospital</name>
      <address>
        <city>Genova</city>
        <zip>I-16184</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angelo Claudio Molinari, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>A. Bianchi Bonomi Hemophilia and Thrombosis Centre IRCCS Ca' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vacant</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Van Creveld Kliniek University Medical Center Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3508 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathelijn Fischer, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Heidi Glosli, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar São João, S. Imuno-hemoterapia</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuela Carvalho, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Unitat Hemofilia Hospital Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olga Benítez Hidalgo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Unidad de Coagulopatías Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Theresa Alvarez Roman, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital General Unidad de Hemofilia 1 Sur Hospitales Universitarios Virgen del Rocio</name>
      <address>
        <city>Seville</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Unidad de Coagulopatias Congenitas Hospital Universitario la Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ana Rosa Cid, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Lund University Hospital</name>
      <address>
        <city>Malmo</city>
        <zip>S-20502</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadine Gretenkort Adersson, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Department of Pediatrics, Clinic of Coag. Disorders Karolinska Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>S-17176</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susanna Ranta, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inselspital Bern, University Children's Hospital</name>
      <address>
        <city>Bern</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jochen Rössler, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Birmingham Children's Hospital NHS Trust - Department of Haematology</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jayashree Motwani, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Hospital for Sick Children</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH9 1LF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Department of Haematology Royal Hospital for Sick Children</name>
      <address>
        <city>Glasgow</city>
        <zip>G 3885</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elizabeth Chalmers, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Haemophila Center Great Ormond Street Hospital for Children</name>
      <address>
        <city>London</city>
        <zip>WC1N3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ri Liesner, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>Finland</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Ireland</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.pednet.eu</url>
    <description>Website of the PedNet Registry</description>
  </link>
  <results_reference>
    <citation>van den Berg HM, Gouw SC, van der Bom JG. Factor VIII products and inhibitors in severe hemophilia A. N Engl J Med. 2013 Apr 11;368(15):1457. doi: 10.1056/NEJMc1301995. No abstract available.</citation>
    <PMID>23574131</PMID>
  </results_reference>
  <results_reference>
    <citation>Gouw SC, van den Berg HM, Fischer K, Auerswald G, Carcao M, Chalmers E, Chambost H, Kurnik K, Liesner R, Petrini P, Platokouki H, Altisent C, Oldenburg J, Nolan B, Garrido RP, Mancuso ME, Rafowicz A, Williams M, Clausen N, Middelburg RA, Ljung R, van der Bom JG; PedNet and Research of Determinants of INhibitor development (RODIN) Study Group. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood. 2013 May 16;121(20):4046-55. doi: 10.1182/blood-2012-09-457036. Epub 2013 Apr 3.</citation>
    <PMID>23553768</PMID>
  </results_reference>
  <results_reference>
    <citation>Carcao MD, van den Berg HM, Ljung R, Mancuso ME; PedNet and the Rodin Study Group. Correlation between phenotype and genotype in a large unselected cohort of children with severe hemophilia A. Blood. 2013 May 9;121(19):3946-52, S1. doi: 10.1182/blood-2012-11-469403. Epub 2013 Mar 12.</citation>
    <PMID>23482934</PMID>
  </results_reference>
  <results_reference>
    <citation>Clausen N, Petrini P, Claeyssens-Donadel S, Gouw SC, Liesner R; PedNet and Research of Determinants of Inhibitor development (RODIN) Study Group. Similar bleeding phenotype in young children with haemophilia A or B: a cohort study. Haemophilia. 2014 Nov;20(6):747-55. doi: 10.1111/hae.12470. Epub 2014 Jun 3.</citation>
    <PMID>24893572</PMID>
  </results_reference>
  <results_reference>
    <citation>Fischer K, Ljung R, Platokouki H, Liesner R, Claeyssens S, Smink E, van den Berg HM. Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry. Haemophilia. 2014 Jul;20(4):e280-6. doi: 10.1111/hae.12448. Epub 2014 May 2.</citation>
    <PMID>24784937</PMID>
  </results_reference>
  <results_reference>
    <citation>Gouw SC, van der Bom JG, Ljung R, Escuriola C, Cid AR, Claeyssens-Donadel S, van Geet C, Kenet G, Makipernaa A, Molinari AC, Muntean W, Kobelt R, Rivard G, Santagostino E, Thomas A, van den Berg HM; PedNet and RODIN Study Group. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013 Jan 17;368(3):231-9. doi: 10.1056/NEJMoa1208024.</citation>
    <PMID>23323899</PMID>
  </results_reference>
  <results_reference>
    <citation>Andersson NG, Auerswald G, Barnes C, Carcao M, Dunn AL, Fijnvandraat K, Hoffmann M, Kavakli K, Kenet G, Kobelt R, Kurnik K, Liesner R, Makipernaa A, Manco-Johnson MJ, Mancuso ME, Molinari AC, Nolan B, Perez Garrido R, Petrini P, Platokouki HE, Shapiro AD, Wu R, Ljung R. Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment. Br J Haematol. 2017 Oct;179(2):298-307. doi: 10.1111/bjh.14844. Epub 2017 Jul 12.</citation>
    <PMID>28699675</PMID>
  </results_reference>
  <results_reference>
    <citation>Mancuso ME, Fischer K, Santagostino E, Oldenburg J, Platokouki H, Konigs C, Escuriola-Ettingshausen C, Rivard GE, Cid AR, Carcao M, Ljung R, Petrini P, Altisent C, Kenet G, Liesner R, Kurnik K, Auerswald G, Chambost H, Makipernaa A, Molinari AC, Williams M, van den Berg HM; European Pediatric Network for Haemophilia Management (PedNet) the REMAIN (REal life MAnagement of children with INhibitors) Study Group. Risk Factors for the Progression from Low to High Titres in 260 Children with Severe Haemophilia A and Newly Developed Inhibitors. Thromb Haemost. 2017 Dec;117(12):2274-2282. doi: 10.1160/TH17-01-0059. Epub 2017 Dec 6.</citation>
    <PMID>29212115</PMID>
  </results_reference>
  <results_reference>
    <citation>Andersson NG, Chalmers EA, Kenet G, Ljung R, Makipernaa A, Chambost H; PedNet Haemophilia Research Foundation. Mode of delivery in hemophilia: vaginal delivery and Cesarean section carry similar risks for intracranial hemorrhages and other major bleeds. Haematologica. 2019 Oct;104(10):2100-2106. doi: 10.3324/haematol.2018.209619. Epub 2019 Feb 21.</citation>
    <PMID>30792204</PMID>
  </results_reference>
  <results_reference>
    <citation>van den Berg HM, Fischer K, Carcao M, Chambost H, Kenet G, Kurnik K, Konigs C, Male C, Santagostino E, Ljung R; PedNet Study Group. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood. 2019 Jul 18;134(3):317-320. doi: 10.1182/blood.2019000658. Epub 2019 Jun 11. No abstract available.</citation>
    <PMID>31186271</PMID>
  </results_reference>
  <results_reference>
    <citation>Male C, Andersson NG, Rafowicz A, Liesner R, Kurnik K, Fischer K, Platokouki H, Santagostino E, Chambost H, Nolan B, Konigs C, Kenet G, Ljung R, Van den Berg M. Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study. Haematologica. 2021 Jan 1;106(1):123-129. doi: 10.3324/haematol.2019.239160.</citation>
    <PMID>31919092</PMID>
  </results_reference>
  <results_reference>
    <citation>van den Berg HM, Mancuso ME, Konigs C, D'Oiron R, Platokouki H, Mikkelsen TS, Motwani J, Nolan B, Santagostino E; European Pediatric Network for Haemophilia Management (PedNet). ITI Treatment is not First-Choice Treatment in Children with Hemophilia A and Low-Responding Inhibitors: Evidence from a PedNet Study. Thromb Haemost. 2020 Aug;120(8):1166-1172. doi: 10.1055/s-0040-1713097. Epub 2020 Jun 22.</citation>
    <PMID>32572865</PMID>
  </results_reference>
  <results_reference>
    <citation>Andersson NG, Wu R, Carcao M, Claeyssens-Donadel S, Kobelt R, Liesner R, Makipernaa A, Ranta S, Ljung R; ICH study group. Long-term follow-up of neonatal intracranial haemorrhage in children with severe haemophilia. Br J Haematol. 2020 Jul;190(2):e101-e104. doi: 10.1111/bjh.16740. Epub 2020 Jun 9. No abstract available.</citation>
    <PMID>32519345</PMID>
  </results_reference>
  <results_reference>
    <citation>Platokouki H, Fischer K, Gouw SC, Rafowicz A, Carcao M, Kenet G, Liesner R, Kurnik K, Rivard GE, van den Berg HM. Vaccinations are not associated with inhibitor development in boys with severe haemophilia A. Haemophilia. 2018 Mar;24(2):283-290. doi: 10.1111/hae.13387. Epub 2017 Dec 15.</citation>
    <PMID>29243367</PMID>
  </results_reference>
  <results_reference>
    <citation>Khair K, Ranta S, Thomas A, Lindvall K; PedNet study group. The impact of clinical practice on the outcome of central venous access devices in children with haemophilia. Haemophilia. 2017 Jul;23(4):e276-e281. doi: 10.1111/hae.13241. Epub 2017 May 24.</citation>
    <PMID>28544163</PMID>
  </results_reference>
  <results_reference>
    <citation>Hashemi SM, Fischer K, Moons KGM, van den Berg HM; PedNet Study group. Validation of the prediction model for inhibitor development in PUPs with severe haemophilia A. Haemophilia. 2016 Mar;22(2):e116-e118. doi: 10.1111/hae.12895. Epub 2016 Feb 8. No abstract available.</citation>
    <PMID>26856685</PMID>
  </results_reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>October 21, 2014</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>September 25, 2020</last_update_submitted>
  <last_update_submitted_qc>September 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>PedNet Haemophilia Research Foundation</investigator_affiliation>
    <investigator_full_name>Marijke van den Berg</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Hemophilia</keyword>
  <keyword>Children, ,</keyword>
  <keyword>Inhibitors,</keyword>
  <keyword>Prophylaxis</keyword>
  <keyword>Long-term outcome</keyword>
  <keyword>Congenital</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
    <mesh_term>Hemophilia B</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/NCT02979119
org study id: Version 6.0 May 2020
nct id: NCT02979119
lead sponsor: 
collaborator: 
has dmc: No
Rationale:

      Haemophilia is a rare disease; to improve knowledge international collaboration is needed.
      Well-defined clinical data will be collected from complete cohorts in order to prevent
      selection bias.

      Objective:

      To collect data on bleeding during neonatal period, endogenous (genetic) and exogenous
      (treatment-related) determinants of inhibitor development and long term outcome.
Design: Multicenter Prospective Observational Birth Cohort Study

      Population:

      Patients with haemophilia A and B with FVIII/IX levels of <1 to 25% born between 1-1-2000 and
      1-1-2030.

      Intervention:

      No intervention; only documentation of patient characteristics and parameters of routine
      patient care and outcome

      Main outcome parameters:

      Outcome: clinically relevant inhibitor development, bleeding pattern and joint status on
      physical examination and imaging.

      Determinants: baseline FVIII/IX levels, measurement of inhibitory antibodies, family history,
      FVIII/IX gene mutation, details on replacement therapy (according to each infusion for the
      first 50 treatment days, and annually thereafter) and surgeries.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

        -  No burden for the patients. Well-defined clinical data will be collected from the
           medical files. Participating in this registry will not change the number of visits to
           the clinic. All outcome parameters that are collected (including laboratory results) are
           part of routine clinical care.

        -  Direct benefit is not to be expected. However, the direct interaction between centres
           that treat patients with rare diseases improves both clinical care and will result in
           better guidelines and as such may provide indirect benefit.

        -  Multicentre participation: haemophilia is a very rare condition. Therefore, collecting
           data on a multi-centre observational cohort is the only way to study this specific
           population.

        -  The registry concerns young boys with haemophilia and cannot be performed in older
           patients, as >90% of inhibitors occur develop during the first 50 exposure days, and the
           results of prophylactic replacement therapy are highly dependent on the initiation of
           this treatment.
observational model: Cohort
time perspective: Prospective
measure: Number of patients with antibody development to exogenous clotting factors
time frame: Until patient reaches age of 18
description: Allo-antibodies against Fact VIII and IX; Blood test: measurement in Bethesda units (BU), positive according to local standards, for most labs >0.5 BU
measure: Long term outcome of haemophilia on joint status using the Hemophilia Joint Health Score (HJHS) and MRI techniques.
time frame: From diagnose every 5 years until patient reaches age of 18
description: Effect of different prophylactic regimen on bleedings and joint damage
measure: Long term outcome different Immune Tolerance Induction (ITI) therapies in patients with inhibitor.
time frame: From date first positive inhibitor titer every 3 years until patient reaches age of 18
description: Effect of different ITI therapies on bleeding and joint damage. Joint damage is assessed using the HJHS and MRI.
arm group label: Cohort I
description: Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX <1%) haemophilia A or B, born from January 1st 2000 until January 1st 2009 who have been or are to be treated with coagulation proteins in one of the participating centres
arm group label: Cohort II
description: Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX <1%) haemophilia A or B, born from January 1st 2009 until January 1st 2020 who have been or are to be treated with coagulation proteins in one of the participating centres
arm group label: Cohort III
description: Children with mild ( FVIII/IX 6 to 25%), moderate (FVIII/IX 1 to 5%) or severe (FVIII/IX <1%) haemophilia A or B, born from January 1st 2020 until January 1st 2030 who have been or are to be treated with coagulation proteins in one of the participating centres
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Rolf Ljung, MD PhD
role: Principal Investigator
affiliation: Lund University Hospital, Malmo, Sweden
last name: H. Marijke Van den Berg, MD PhD
role: Study Director
affiliation: University Medical Center Utrecht, The Netherlands
last name: H. Marijke van den Berg, MD, PhD
phone: +31850299993
email: h.marijke.vandenberg@pednet.eu
last name: Ella van Hardeveld, MANP
phone: +31850299993
email: e.m.vanhardeveld@pednet.eu
facility: 
status: Completed
facility: 
status: Recruiting
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status: Not yet recruiting
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country: Austria
country: Belgium
country: Canada
country: Czechia
country: Denmark
country: Finland
country: France
country: Germany
country: Greece
country: Ireland
country: Israel
country: Italy
country: Netherlands
country: Norway
country: Portugal
country: Spain
country: Sweden
country: Switzerland
country: United Kingdom
url: http://www.pednet.eu
description: Website of the PedNet Registry
citation: van den Berg HM, Gouw SC, van der Bom JG. Factor VIII products and inhibitors in severe hemophilia A. N Engl J Med. 2013 Apr 11;368(15):1457. doi: 10.1056/NEJMc1301995. No abstract available.
PMID: 23574131
citation: Gouw SC, van den Berg HM, Fischer K, Auerswald G, Carcao M, Chalmers E, Chambost H, Kurnik K, Liesner R, Petrini P, Platokouki H, Altisent C, Oldenburg J, Nolan B, Garrido RP, Mancuso ME, Rafowicz A, Williams M, Clausen N, Middelburg RA, Ljung R, van der Bom JG; PedNet and Research of Determinants of INhibitor development (RODIN) Study Group. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood. 2013 May 16;121(20):4046-55. doi: 10.1182/blood-2012-09-457036. Epub 2013 Apr 3.
PMID: 23553768
citation: Carcao MD, van den Berg HM, Ljung R, Mancuso ME; PedNet and the Rodin Study Group. Correlation between phenotype and genotype in a large unselected cohort of children with severe hemophilia A. Blood. 2013 May 9;121(19):3946-52, S1. doi: 10.1182/blood-2012-11-469403. Epub 2013 Mar 12.
PMID: 23482934
citation: Clausen N, Petrini P, Claeyssens-Donadel S, Gouw SC, Liesner R; PedNet and Research of Determinants of Inhibitor development (RODIN) Study Group. Similar bleeding phenotype in young children with haemophilia A or B: a cohort study. Haemophilia. 2014 Nov;20(6):747-55. doi: 10.1111/hae.12470. Epub 2014 Jun 3.
PMID: 24893572
citation: Fischer K, Ljung R, Platokouki H, Liesner R, Claeyssens S, Smink E, van den Berg HM. Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry. Haemophilia. 2014 Jul;20(4):e280-6. doi: 10.1111/hae.12448. Epub 2014 May 2.
PMID: 24784937
citation: Gouw SC, van der Bom JG, Ljung R, Escuriola C, Cid AR, Claeyssens-Donadel S, van Geet C, Kenet G, Makipernaa A, Molinari AC, Muntean W, Kobelt R, Rivard G, Santagostino E, Thomas A, van den Berg HM; PedNet and RODIN Study Group. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013 Jan 17;368(3):231-9. doi: 10.1056/NEJMoa1208024.
PMID: 23323899
citation: Andersson NG, Auerswald G, Barnes C, Carcao M, Dunn AL, Fijnvandraat K, Hoffmann M, Kavakli K, Kenet G, Kobelt R, Kurnik K, Liesner R, Makipernaa A, Manco-Johnson MJ, Mancuso ME, Molinari AC, Nolan B, Perez Garrido R, Petrini P, Platokouki HE, Shapiro AD, Wu R, Ljung R. Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment. Br J Haematol. 2017 Oct;179(2):298-307. doi: 10.1111/bjh.14844. Epub 2017 Jul 12.
PMID: 28699675
citation: Mancuso ME, Fischer K, Santagostino E, Oldenburg J, Platokouki H, Konigs C, Escuriola-Ettingshausen C, Rivard GE, Cid AR, Carcao M, Ljung R, Petrini P, Altisent C, Kenet G, Liesner R, Kurnik K, Auerswald G, Chambost H, Makipernaa A, Molinari AC, Williams M, van den Berg HM; European Pediatric Network for Haemophilia Management (PedNet) the REMAIN (REal life MAnagement of children with INhibitors) Study Group. Risk Factors for the Progression from Low to High Titres in 260 Children with Severe Haemophilia A and Newly Developed Inhibitors. Thromb Haemost. 2017 Dec;117(12):2274-2282. doi: 10.1160/TH17-01-0059. Epub 2017 Dec 6.
PMID: 29212115
citation: Andersson NG, Chalmers EA, Kenet G, Ljung R, Makipernaa A, Chambost H; PedNet Haemophilia Research Foundation. Mode of delivery in hemophilia: vaginal delivery and Cesarean section carry similar risks for intracranial hemorrhages and other major bleeds. Haematologica. 2019 Oct;104(10):2100-2106. doi: 10.3324/haematol.2018.209619. Epub 2019 Feb 21.
PMID: 30792204
citation: van den Berg HM, Fischer K, Carcao M, Chambost H, Kenet G, Kurnik K, Konigs C, Male C, Santagostino E, Ljung R; PedNet Study Group. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood. 2019 Jul 18;134(3):317-320. doi: 10.1182/blood.2019000658. Epub 2019 Jun 11. No abstract available.
PMID: 31186271
citation: Male C, Andersson NG, Rafowicz A, Liesner R, Kurnik K, Fischer K, Platokouki H, Santagostino E, Chambost H, Nolan B, Konigs C, Kenet G, Ljung R, Van den Berg M. Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study. Haematologica. 2021 Jan 1;106(1):123-129. doi: 10.3324/haematol.2019.239160.
PMID: 31919092
citation: van den Berg HM, Mancuso ME, Konigs C, D'Oiron R, Platokouki H, Mikkelsen TS, Motwani J, Nolan B, Santagostino E; European Pediatric Network for Haemophilia Management (PedNet). ITI Treatment is not First-Choice Treatment in Children with Hemophilia A and Low-Responding Inhibitors: Evidence from a PedNet Study. Thromb Haemost. 2020 Aug;120(8):1166-1172. doi: 10.1055/s-0040-1713097. Epub 2020 Jun 22.
PMID: 32572865
citation: Andersson NG, Wu R, Carcao M, Claeyssens-Donadel S, Kobelt R, Liesner R, Makipernaa A, Ranta S, Ljung R; ICH study group. Long-term follow-up of neonatal intracranial haemorrhage in children with severe haemophilia. Br J Haematol. 2020 Jul;190(2):e101-e104. doi: 10.1111/bjh.16740. Epub 2020 Jun 9. No abstract available.
PMID: 32519345
citation: Platokouki H, Fischer K, Gouw SC, Rafowicz A, Carcao M, Kenet G, Liesner R, Kurnik K, Rivard GE, van den Berg HM. Vaccinations are not associated with inhibitor development in boys with severe haemophilia A. Haemophilia. 2018 Mar;24(2):283-290. doi: 10.1111/hae.13387. Epub 2017 Dec 15.
PMID: 29243367
citation: Khair K, Ranta S, Thomas A, Lindvall K; PedNet study group. The impact of clinical practice on the outcome of central venous access devices in children with haemophilia. Haemophilia. 2017 Jul;23(4):e276-e281. doi: 10.1111/hae.13241. Epub 2017 May 24.
PMID: 28544163
citation: Hashemi SM, Fischer K, Moons KGM, van den Berg HM; PedNet Study group. Validation of the prediction model for inhibitor development in PUPs with severe haemophilia A. Haemophilia. 2016 Mar;22(2):e116-e118. doi: 10.1111/hae.12895. Epub 2016 Feb 8. No abstract available.
PMID: 26856685
responsible party type: Principal Investigator
investigator affiliation: PedNet Haemophilia Research Foundation
investigator full name: Marijke van den Berg
investigator title: Director
mesh term: Hemophilia A
mesh term: Hemophilia B
sharing ipd: No