Clinical trial NCT00510042: National Study of Moderate and Severe Von Willebrand Disease in the Netherlands
Official title: National Study of Moderate and Severe Von Willebrand Disease in the Netherlands
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Von Willebrand Disease
Keywords: von Willebrand disease
von Willebrand factor
national study
bleeding disorder
quality of life
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Foundation Haemophilia
name: CSL Behring
First posted: 2007-08-01
Enrollment: 1100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with moderate and devere von Willebrand disease, known in a hemophilia treatment center

Brief summary: The objective of this study is to assess the clinical presentation, the treatment and the complications of the disease and treatment in moderate and severe von Willebrand disease. Another goal is to investigate the influence of von Willebrand disease on quality of life.

Detailed description: The incidence of von Willebrand disease in the Netherlands is unknown, but the occurrence of all types of von Willebrand disease together is estimated at 1:100-1:200 individuals. Most patients have mild von Willebrand disease, mostly type 1. For the more severe forms of von Willebrand disease the incidence in unclear, but the expectation is, that there are at least 500-1500 patients. In the Netherlands, an unique situation exists for the treatment of patients with hemophilia and related coagulation disorders. In 2000 a hemophilia management policy was set up by the Ministry of Health, which stated that the care for these patients should be concentrated in 13 Hemophilia Treatment Centers (HTC). The representatives of the attending centers, the hemophilia specialists, are organized in the NVHB, the Dutch society of Hemophilia treaters. In the hemophilia management policy is stated that all patients with a coagulation disorder dependent of replacement products must be treated in a HTC or under responsibility of a HTC. These patients are seen in a HTC at least once a year.

Because all moderate and severe von Willebrand patients in the Netherlands are known in HTC, it is possible to register and study this population. This is imperative to the research of von Willebrand disease. Because the moderate and severe forms of von Willebrand disease are rare, it is impossible for an individual center to perform research of moderate severe and severe von Willebrand disease. Therefore a national approach is necessary.

For optimal care of patients with the moderate and severe form of von Willebrand disease a better understanding of symptoms, diagnostics, treatment and complications of treatment is necessary. The present study aims to register and investigate all patients in the Netherlands with moderate and severe von Willebrand disease to gain understanding of the clinical presentation, the treatment and the complications of treatment in moderate and severe von Willebrand disease. Another goal is to investigate the influence of von Willebrand disease on quality of life.

To answer these questions a questionnaire is developed, which will be sent to the study population. In addition, blood will be drawn for von Willebrand factor measurement and plasma and DNA will be stored. The relationship between laboratory parameters, (including von Willebrand factor, FVIII and prothrombotic coagulation disorders) and the clinical phenotype in patients with moderate and severe von Willebrand disease will be studied. We will assess the effect of the laboratory parameters on both the severity of bleeding tendency, and the possible protecting effect on the risk of arterial thrombosis. In the future mutation analysis of the VWF gene will be performed in patients with moderate and severe von Willebrand disease in the Netherlands.

Eligibility criteria: Inclusion Criteria:

1. haemorrhagic symptoms or a family history of von Willebrand disease
2. vWF antigen ≤ 30%, lowest measurement counts and/or vWF activity (vWF:RCo of vWF:CB) ≤ 30%, lowest measurement counts and/or FVIII:C ≤ 40 %, lowest measurement counts
3. being known in a hemophilia treatment center or if only the diagnose is made in a hemophilia treatment center this must be done after 1987

Exclusion Criteria:

1. Hemophilia A
2. Carriership of hemophilia A
3. No informed consent

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center Amsterdam
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Den Haag
country: Netherlands
facility: Haga Hospital
city: Eindhoven
country: Netherlands
facility: Maxima Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Haarlem
country: Netherlands
facility: Kennemer Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academic Hospital Maastricht
city: Nijmegen
country: Netherlands
facility: University Medical Center St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht Van Creveldkliniek
Study officials:
affiliation: Erasmus Medical Center
name: Eva M de Wee, MD
role: STUDY_DIRECTOR
affiliation: Erasmus Medical Center
name: Frank WG Leebeek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Karin Fijn van Draat, MD, PhD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: Jeroen CJ Eikenboom, MD, PhD
role: STUDY_CHAIR
affiliation: Erasmus Medical Center
name: Arja de Goede-Bolder, MD
role: STUDY_CHAIR
affiliation: Van Creveldkliniek, University Medical Center Utrecht
name: Eveline P Mauser-Bunschoten, MD, PhD
role: STUDY_CHAIR
affiliation: University Medical Center Goningen
name: Karina Meijer, MD, PhD
role: STUDY_CHAIR
affiliation: University Medical Center St. Radboud Nijmegen
name: Britta Laros-van Gorkom, MD, PhD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: Johanna G van der Bom, PhD
role: STUDY_CHAIR
affiliation: Organization for Hemophilia Patients
name: Manon A Degenaar-Dujardin, BA
role: STUDY_CHAIR
References:
citation: Mannucci PM. Treatment of von Willebrand's Disease. N Engl J Med. 2004 Aug 12;351(7):683-94. doi: 10.1056/NEJMra040403. No abstract available.
citation: Sadler JE, Mannucci PM, Berntorp E, Bochkov N, Boulyjenkov V, Ginsburg D, Meyer D, Peake I, Rodeghiero F, Srivastava A. Impact, diagnosis and treatment of von Willebrand disease. Thromb Haemost. 2000 Aug;84(2):160-74. No abstract available.
citation: Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1994 Apr;71(4):520-5.
citation: Tosetto A, Rodeghiero F, Castaman G, Goodeve A, Federici AB, Batlle J, Meyer D, Fressinaud E, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J, Hill F, Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost. 2006 Apr;4(4):766-73. doi: 10.1111/j.1538-7836.2006.01847.x.
citation: Federici AB. Clinical diagnosis of von Willebrand disease. Haemophilia. 2004 Oct;10 Suppl 4:169-76. doi: 10.1111/j.1365-2516.2004.00991.x.