Clinical trial NCT03623295: The Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B
Official title: The Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2018-08-09
Enrollment: 304
Sex: MALE
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Patients will be recruited from Hemophilia Treatment Centers participating in the INSIGHT consortium, a well-established and productive group of investigators from European countries, Canada and Australia.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Bleeding phenotype
timeFrame: Retrospective 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Multiple Locations
country: Belgium
facility: Multicentre: Leuven, Brussels
city: Multiple Locations
country: Canada
facility: Multicentre: Vancouver, Toronto, Hamilton
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Multiple Locations
country: Germany
facility: Multicentre: Bonn, Berlin, Frankfurt, München, Hamburg
city: Multiple Locations
country: Italy
facility: Multicentre: Florence, Rome, Parma, Milan, Turin
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: Utrecht University Medical Center
city: Veldhoven
country: Netherlands
facility: Máxima Medical Center
city: Multiple Locations
country: Spain
facility: Multicentre: Valencia, Madrid, Barcelona
city: Multiple Locations
country: United Kingdom
facility: Multicentre: Manchester, London, Liverpool, Glasgow, Cardiff, Sheffield
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Karin Fijnvandraat
role: PRINCIPAL_INVESTIGATOR
References: