Clinical trial NCT02979119: The European Paediatric Network for Haemophilia Management ( PedNet Registry)
Official title: The European Paediatric Network for Haemophilia Management and the PedNet Haemophilia Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Factor VIII Deficiency
Factor IX Deficiency
Keywords: Hemophilia
Children
Inhibitors
Prophylaxis
Long-term outcome
Congenital
Lead sponsor: PedNet Haemophilia Research Foundation
Sponsor class: OTHER
First posted: 2016-12-01
Enrollment: 4000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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 2030 who have been or are to be treated in one of the participating centres

Brief summary: 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.

Detailed description: 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 and girls 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with Haemophilia A or B
* Factor VIII/ IX activity of \<1 to 25%
* Complete records of Factor treatment and bleeds
* Treated in one of the participating centres

Exclusion Criteria:

* Patients referred because of an inhibitor\*
* Informed consent not obtained

Primary outcomes:
measure: Number of patients with antibody development to exogenous clotting factors
timeFrame: Until patient reaches age of 18
Secondary outcomes:
measure: Long term outcome of haemophilia on joint status using the Hemophilia Joint Health Score (HJHS) and MRI techniques.
timeFrame: From diagnose every 5 years until patient reaches age of 18
measure: Long term outcome different Immune Tolerance Induction (ITI) therapies in patients with inhibitor.
timeFrame: From date first positive inhibitor titer preferably every 3 years until patient reaches age of 18
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitäts-Klinik für Kinder- und Jugendheilkunde
city: Vienna
country: Austria
facility: Medical University of Vienna - Department of Paediatrics
city: Leuven
country: Belgium
facility: Service of Pediatric Haematology University Hospital Leuven
city: Montréal
country: Canada
facility: Division of Hematology/Oncology Hôpital St Justine
city: Toronto
country: Canada
facility: Division of Haematology/Oncology Hospital for Sick Children
city: Brno
country: Czechia
facility: Haemophilia Comprehensive Care Centre, Centre for Thrombosis and Haemostasis Children's University Hospital Brno
city: Praha
country: Czechia
facility: Department of Paediatric Haematology/oncology - University Hospital Motol
city: Aarhus
country: Denmark
facility: Department of Pediatrics Århus Kommunehospital Skejby Sygehus
city: Helsinki
country: Finland
facility: Children's Hospital Helsinki University Hospital
city: Le Kremlin Bicêtre
country: France
facility: Service Hématologique Centre Regional Traitement d'Hemophilie Bicetre
city: Marseille Cedex-05
country: France
facility: Service d'Hématologie Pédiatrique Hôpital Universitaire La Timone
city: Toulouse
country: France
facility: Centre de traitement des hémophiles Hôpital Universitaire Purpan
city: Berlin
country: Germany
facility: Charité Campus Virchow Klinikum, Klinik für Pädiatrie m.S. Onkologie und Hämatologie
city: Berlin
country: Germany
facility: Department of Internal Medicine, Hemophilia Treatment Center, Vivantes Klinikum im Friedrichshain
city: Bonn
country: Germany
facility: Institut für Experimentelle Hämatologie und Transfusionsmedizin Universitätsklinikum Bonn
city: Bremen
country: Germany
facility: Klinik Bremen-Mitte Prof.-Hess-Kinderklinik
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt & Goethe University - Clinical and Molecular Hemostasis, Department of Pediatrics
city: Munich
country: Germany
facility: Dr. v. Haunersches Kinderspital University of Munich
city: Mörfelden-Walldorf
country: Germany
facility: Hämophilie Zentrum Rhein Main
city: Athens
country: Greece
facility: Haemophilia-Haemostasis Unit St. Sophia Children's Hospital
city: Dublin
country: Ireland
facility: Dept of Paediatric Haematology Our Lady's Children's Hospital for Sick Children Crumlin
city: Ramat Gan
country: Israel
facility: The National Hemophilia Center Sheba Medical Center, Tel Hashomer
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Genova
country: Italy
facility: Gaslini Hospital
city: Milano
country: Italy
facility: A. Bianchi Bonomi Hemophilia and Thrombosis Centre IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Utrecht
country: Netherlands
facility: Van Creveld Kliniek University Medical Center Utrecht
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Porto
country: Portugal
facility: Centro Hospitalar São João, S. Imuno-hemoterapia
city: Barcelona
country: Spain
facility: Unitat Hemofilia Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Unidad de Coagulopatías Hospital Universitario La Paz
city: Seville
country: Spain
facility: Hospital General Unidad de Hemofilia 1 Sur Hospitales Universitarios Virgen del Rocio
city: Valencia
country: Spain
facility: Unidad de Coagulopatias Congenitas Hospital Universitario la Fe
city: Malmo
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Department of Pediatrics, Clinic of Coag. Disorders Karolinska Hospital
city: Bern
country: Switzerland
facility: Inselspital Bern, University Children's Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Trust - Department of Haematology
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
city: Glasgow
country: United Kingdom
facility: Department of Haematology Royal Hospital for Sick Children
city: London
country: United Kingdom
facility: Haemophila Center Great Ormond Street Hospital for Children
Study officials:
affiliation: The National Hemophilia Center Ministry of Health Sheba Medical Center Ramat Gan, Israel
name: Gili Kenet, PhD, MD
role: STUDY_DIRECTOR
affiliation: Medical University of Vienna
name: Christoph Male, MD
role: STUDY_CHAIR
affiliation: The National Hemophilia Center Ministry of Health Sheba Medical Center Ramat Gan, Israel
name: Gili Kenet, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
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