The European Paediatric Network for Haemophilia Management ( PedNet Registry)

Study Overview
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Brief Summary
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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
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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.

Official Title
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The European Paediatric Network for Haemophilia Management and the PedNet Haemophilia Registry

Conditions
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Factor VIII Deficiency, Factor IX Deficiency

Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort I<br>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 December 31st 2009 who have been or are to be treated with coagulation proteins in one of the participating centres | |
| Cohort II<br>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 2010 until December 31st 2019 who have been or are to be treated with coagulation proteins in one of the participating centres | |
| Cohort III<br>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 December 31st 2029 who have been or are to be treated with coagulation proteins in one of the participating centres | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with antibody development to exogenous clotting factors | Allo-antibodies against Factor VIII and IX; Blood test: measurement in Bethesda units (BU), positive according to local standards, for most labs >0.5 BU | Until patient reaches age of 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term outcome of haemophilia on joint status using the Hemophilia Joint Health Score (HJHS) and MRI techniques. | Effect of different prophylactic regimen on bleeding and joint damage | From diagnose every 5 years until patient reaches age of 18 | 
| Long term outcome different Immune Tolerance Induction (ITI) therapies in patients with inhibitor. | Effect of different ITI therapies on bleeding and joint damage. Joint damage is assessed using the HJHS and MRI. | From date first positive inhibitor titer preferably every 3 years until patient reaches age of 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia, Children, Inhibitors, Prophylaxis, Long-term outcome, Congenital