The Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B

NCT ID: NCT03623295

Last Updated: 2025-04-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

304 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-01-01

Study Completion Date

2021-10-01

Brief Summary

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There are large inter-individual differences in the bleeding pattern of patients with moderate or mild hemophilia. The major determinant of bleeding phenotype is the level of coagulant factor VIII or IX. In hemophilia A, studies addressing the association between factor VIII level and the clinical bleeding pattern yield conflicting results. In hemophilia B such studies have not yet been performed.

The primary aim of this project is to analyze the association between factor VIII and factor IX levels and the bleeding phenotype. The secondary aim is to analyze potential differences in phenotype between hemophilia A and B.

The project is a multicentre observational cohort study. We will include 230 patients with moderate or mild hemophilia A or B (FVIII/FIX 0.02-0.35 IU/mL) who are 12 to 55 years old. The main cohort study consists of clinical data collection, one blood sample and an online questionnaire for patients. Data will be collected on the nature and duration of all bleeding episodes, disease and treatment characteristics, physical activity level and musculoskeletal status. One blood withdrawal will be performed for centralized laboratory assays for FVIII or FIX levels (both one-stage and chromogenic assays) and genetic analysis for the most prevalent prothrombotic mutations. The online questionnaire for patients focuses on bleeds experienced in the past.

A subset of 50 patients aged 24 years or older with mild and moderate hemophilia A will be investigated in more detail by longitudinal data collection including analysis of physical joint status, MRI imaging of joints and biomarkers for joint damage. This longitudinal observation will consist of two time points that lie two years apart, allowing us to identify any changes that occur over the observed time period with respect to joint status.

Detailed Description

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Conditions

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Hemophilia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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Cohort study population

For the main cohort study, we will include 230 patients with moderate or mild hemophilia A or B.

Blood sample

Intervention Type OTHER

Blood withdrawal.

Questionnaire

Intervention Type OTHER

Online questionnaire about the bleeds that patients experienced in the past.

Sub study population

A subset of 50 patients of the cohort study population will be investigated in more detail by longitudinal data collection.

Blood sample

Intervention Type OTHER

Blood withdrawal.

MRI-imaging

Intervention Type OTHER

MRI imaging of joints.

Physical examination

Intervention Type OTHER

Physical examination of joint status.

Interventions

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Blood sample

Blood withdrawal.

Intervention Type OTHER

Questionnaire

Online questionnaire about the bleeds that patients experienced in the past.

Intervention Type OTHER

MRI-imaging

MRI imaging of joints.

Intervention Type OTHER

Physical examination

Physical examination of joint status.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Moderate or mild hemophilia A (FVIII:C 0.02-0.35 IU/mL) or hemophilia B (FIX:C 0.02-0.35 IU/mL)
* Age from 12 up to and including 55 years

Exclusion Criteria

* Other clotting disorder
* Participation in another trial with an investigational product
* Comorbidity affecting the musculoskeletal status
* Clinically relevant inhibitor status at present or in the past
* Hemophilia B Leyden
* Use of anticoagulants
Minimum Eligible Age

12 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role lead

Responsible Party

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Karin Fijnvandraat

Professor of Pediatric Hematology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Karin Fijnvandraat

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

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Royal Adelaide Hospital

Adelaide, , Australia

Site Status

Medical University of Vienna

Vienna, , Austria

Site Status

Multicentre: Leuven, Brussels

Multiple Locations, , Belgium

Site Status

Multicentre: Vancouver, Toronto, Hamilton

Multiple Locations, , Canada

Site Status

Helsinki University Central Hospital

Helsinki, , Finland

Site Status

Multicentre: Bonn, Berlin, Frankfurt, München, Hamburg

Multiple Locations, , Germany

Site Status

Multicentre: Florence, Rome, Parma, Milan, Turin

Multiple Locations, , Italy

Site Status

Academic Medical Center

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

Utrecht University Medical Center

Utrecht, , Netherlands

Site Status

Máxima Medical Center

Veldhoven, , Netherlands

Site Status

Multicentre: Valencia, Madrid, Barcelona

Multiple Locations, , Spain

Site Status

Multicentre: Manchester, London, Liverpool, Glasgow, Cardiff, Sheffield

Multiple Locations, , United Kingdom

Site Status

Countries

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Australia Austria Belgium Canada Finland Germany Italy Netherlands Spain United Kingdom

Other Identifiers

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NL61564.018.17

Identifier Type: -

Identifier Source: org_study_id

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