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

NCT03623295 | Completed

• 1 other identifier: NL61564.018.17
• Study Type: observational
• Target: 304
• Locations: 9 countries
• Sites: 16

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.

Conditions

Hemophilia

Outcome Measures

Primary Outcomes (1)

• Bleeding phenotype

  Annual bleeding rate, annual major bleeding rate, annual spontaneous joint bleeding rate, annual joint bleeding rate

  Retrospective 10 years

Study Arms (2)

Cohort study population

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

Other: Blood sample; Other: Questionnaire

Sub study population

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

Other: Blood sample; Other: MRI-imaging; Other: Physical examination

Interventions

Blood sample OTHER

Blood withdrawal.

Cohort study population; Sub study population

Questionnaire OTHER

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

Cohort study population

MRI-imaging OTHER

MRI imaging of joints.

Sub study population

Physical examination OTHER

Physical examination of joint status.

Sub study population

Eligibility Criteria

• Age: 12 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (17)

Royal Adelaide Hospital

Adelaide, Australia

Location

Medical University of Vienna

Vienna, Austria

Location

Multicentre: Leuven, Brussels

Multiple Locations, Belgium

Location

Multicentre: Vancouver, Toronto, Hamilton

Multiple Locations, Canada

Location

Helsinki University Central Hospital

Helsinki, Finland

Location

Multicentre: Bonn, Berlin, Frankfurt, München, Hamburg

Multiple Locations, Germany

Location

Multicentre: Florence, Rome, Parma, Milan, Turin

Multiple Locations, Italy

Location

Academic Medical Center

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Utrecht University Medical Center

Utrecht, Netherlands

Location

Máxima Medical Center

Veldhoven, Netherlands

Location

Multicentre: Valencia, Madrid, Barcelona

Multiple Locations, Spain

Location

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

Multiple Locations, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimens to be retained for future research: * Blood * Urine

MeSH Terms

Conditions

Hemophilia A

Interventions

Blood Specimen Collection; Surveys and Questionnaires; Restraint, Physical

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Behavior Control; Therapeutics; Immobilization

Study Officials

• Karin Fijnvandraat

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatric Hematology

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 9, 2018
• Study Start: January 1, 2018
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: April 30, 2025

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CA (1); NL (8); FI (1); GB (1); BE (1); DE (1); IT (1); ES (1)