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

Completed

• Conditions: Hemophilia
• Interventions: Other: Blood sample; Other: MRI-imaging; Other: Questionnaire; Other: Physical examination

• Registration Number: NCT03623295
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

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

Not available

Study Timeline

• Study Start: 2018-01-01
• Study First Submitted: 2018-08-06
• Study First Submitted QC: 2018-08-06
• Study First Posted: 2018-08-09
• Status Verified: 2021-10
• Primary Completion: 2021-10-01
• Study Completion: 2021-10-01
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 304

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Sub study population	Physical examination	A subset of 200 patients of the cohort study population will be investigated in more detail by longitudinal data collection.
Sub study population	Blood sample	A subset of 200 patients of the cohort study population will be investigated in more detail by longitudinal data collection.
Sub study population	MRI-imaging	A subset of 200 patients of the cohort study population will be investigated in more detail by longitudinal data collection.
Cohort study population	Blood sample	For the main cohort study, we will include 500 patients with moderate or mild hemophilia A and 500 patients with moderate or mild hemophilia B.
Cohort study population	Questionnaire	For the main cohort study, we will include 500 patients with moderate or mild hemophilia A and 500 patients with moderate or mild hemophilia B.

Primary Outcome Measures

Name	Time	Method
Bleeding phenotype	Retrospective 10 years	Annual bleeding rate, annual major bleeding rate, annual spontaneous joint bleeding rate, annual joint bleeding rate

Trial Locations

Locations (17)

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Medical University of Vienna; 🇦🇹 Vienna, Austria

Multicentre: Leuven, Brussels; 🇧🇪 Multiple Locations, Belgium

Multicentre: Vancouver, Toronto, Hamilton; 🇨🇦 Multiple Locations, Canada

Helsinki University Central Hospital; 🇫🇮 Helsinki, Finland

Multicentre: Bonn, Berlin, Frankfurt, München, Hamburg; 🇩🇪 Multiple Locations, Germany

Multicentre: Florence, Rome, Parma, Milan, Turin; 🇮🇹 Multiple Locations, Italy

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Maastricht University Medical Center; 🇳🇱 Maastricht, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

Utrecht University Medical Center; 🇳🇱 Utrecht, Netherlands

Máxima Medical Center; 🇳🇱 Veldhoven, Netherlands

Multicentre: Valencia, Madrid, Barcelona; 🇪🇸 Multiple Locations, Spain

Multicentre: Manchester, London, Liverpool, Glasgow, Cardiff, Sheffield; 🇬🇧 Multiple Locations, United Kingdom