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

Hemophilia Clinical Trial

— DYNAMO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03623295
• Other study ID #: NL61564.018.17
• Status: Recruiting
• Start date: January 1, 2018
• Est. completion date: April 1, 2022

Study information

• Verified date: August 2018
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Anne-Fleur Zwagemaker
• Phone: +31205668668
• Email: a.zwagemaker[@]amc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 500 patients with moderate or mild hemophilia A (FVIII 0.02-0.35 IU/mL) and 500 patients with moderate or mild hemophilia B (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 200 patients aged 24 years or older (100 with moderate or mild hemophilia A and 100 with moderate or mild hemophilia B) 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: April 1, 2022
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Other:
• Blood sample
Blood withdrawal.
• Questionnaire
Online questionnaire about the bleeds that patients experienced in the past.
• MRI-imaging
MRI imaging of joints.
• Physical examination
Physical examination of joint status.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Austria	Medical University of Vienna	Vienna
Belgium	Multicentre: Leuven, Brussels	Multiple Locations
Canada	Multicentre: Vancouver, Toronto, Hamilton	Multiple Locations
Finland	Helsinki University Central Hospital	Helsinki
Germany	Multicentre: Bonn, Berlin, Frankfurt, München, Hamburg	Multiple Locations
Italy	Multicentre: Florence, Rome, Parma, Milan, Turin	Multiple Locations
Netherlands	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
Spain	Multicentre: Valencia, Madrid, Barcelona	Multiple Locations
United Kingdom	Multicentre: Manchester, London, Liverpool, Glasgow, Cardiff, Sheffield	Multiple Locations

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Canada,  Finland,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bleeding phenotype	Annual bleeding rate, annual major bleeding rate, annual spontaneous joint bleeding rate, annual joint bleeding rate	Retrospective 10 years