Clinical trial NCT03521583: Von Willebrand Disease in the Netherlands
Official title: Von Willebrand Disease in the Netherlands - Prospective Study (WiN-Pro)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Von Willebrand Disease
Keywords: von Willebrand disease
von Willebrand factor
Nationwide study
Prospective study
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Stichting Haemophilia (Dutch Haemophilia Foundation)
name: CSL Behring
name: Shire
First posted: 2018-05-11
Enrollment: 1100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Von Willebrand disease patients known in a Hemophilia Treatment Center in the Netherlands

Brief summary: The primary aim of this study is to prospectively investigate the current bleeding tendency of children and adults with VWD.

Detailed description: Von Willebrand disease (VWD) is the most common inherited bleeding disorder, and is characterized by a defective platelet adhesion and aggregation. VWD is caused by a reduced (type 1), an abnormal function (type 2) or a complete absence (type 3) of von Willebrand factor (VWF).

In recent years, large retrospective cohort studies have provided valuable insights on the clinical presentation, bleeding phenotype, quality of life, diagnostics, genetics and treatment of patients with VWD. One of these large studies is the von Willebrand in the Netherlands (WiN) study, which is a nationwide cross sectional study of moderate and severe von Willebrand disease patients, that was initiated in 2007. Over 800 VWD patients were included in the WiN study, which was about 80% of all known VWD patients in the Netherlands. Although the WiN study and large retrospective studies in other countries provided important insights in understanding VWD, some significant challenges remain and large prospective studies are lacking to provide answers.

All large retrospective cohort studies have assessed the bleeding phenotype of patients with VWD using bleeding scores or retrospective questionnaires. Bleeding scores calculate the sum of all bleeding episodes during lifetime. Therefore, they provide useful information on the bleeding tendency during lifetime. However, bleeding scores do not provide information on the change of bleeding tendency. If a patient had a period in his or her lifetime in which he or she had many bleeding episodes, then the bleeding score is high. Though, the patient could have had those bleeds 30 years ago and did not have a bleeding episode since then. Therefore, bleeding scores do not provide information on the current bleeding phenotype of VWD patients. Furthermore, previous studies provided limited information on the frequency of mild bleedings, like gum bleeding or epistaxis, that occur in daily life but do not require therapy. Nevertheless, these bleeding episodes can cause a major impairment in quality of life. This is especially important in children, because school-going children with VWD have a lower quality of life and have a different bleeding tendency, characterized by more cutaneous bleeding (81%), oropharyngeal bleeding (64%) and epistaxis (56%).

Therefore, the primary aim of this study is to prospectively investigate the current bleeding tendency of children and adults with VWD.

Eligibility criteria: Inclusion Criteria:

* Historically lowest VWF:Ag and/or VWF:RCo and/or VWF:CB ≤ 0.30 IU/mL and/or FVIII:C ≤ 0.40 IU/mL
* Treatment at a Hemophilia treatment center in the Netherlands
* All types of VWD
* All ages

Exclusion Criteria:

- Other known bleeding disorders present.

Primary outcomes:
measure: Bleeding rate
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
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: 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 University Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: Erasmus Medical Center
name: Frank WG Leebeek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center
name: Ferdows Atiq, MD
role: STUDY_DIRECTOR
affiliation: Erasmus Medical Center
name: Marjon H Cnossen, MD, PhD
role: STUDY_CHAIR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Karin Fijnvandraat, MD, PhD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: Jeroen Eikenboom, MD, PhD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: Johanna G van der Bom, PhD
role: STUDY_CHAIR
affiliation: Radboud University Medical Center
name: Britta AP Laros-van Gorkom, MD, PhD
role: STUDY_CHAIR
affiliation: University Medical Center Groningen
name: Karina Meijer, MD, PhD
role: STUDY_CHAIR
affiliation: UMC Utrecht
name: Karin PM van Galen, MD, PhD
role: STUDY_CHAIR
affiliation: Netherlands Hemophilia Society
name: Joke de Meris
role: STUDY_CHAIR
References:
citation: Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med. 2016 Nov 24;375(21):2067-2080. doi: 10.1056/NEJMra1601561. No abstract available.
citation: Sanders YV, Groeneveld D, Meijer K, Fijnvandraat K, Cnossen MH, van der Bom JG, Coppens M, de Meris J, Laros-van Gorkom BA, Mauser-Bunschoten EP, Leebeek FW, Eikenboom J; WiN study group. von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease. Blood. 2015 May 7;125(19):3006-13. doi: 10.1182/blood-2014-09-603241. Epub 2015 Feb 11.
citation: de Wee EM, Mauser-Bunschoten EP, Van Der Bom JG, Degenaar-Dujardin ME, Eikenboom HC, Fijnvandraat K, de Goede-Bolder A, Laros-van Gorkom BA, Meijer K, Raat H, Leebeek FW; Win Study Group. Health-related quality of life among adult patients with moderate and severe von Willebrand disease. J Thromb Haemost. 2010 Jul;8(7):1492-9. doi: 10.1111/j.1538-7836.2010.03864.x. Epub 2010 Mar 23.
citation: de Wee EM, Sanders YV, Mauser-Bunschoten EP, van der Bom JG, Degenaar-Dujardin ME, Eikenboom J, de Goede-Bolder A, Laros-van Gorkom BA, Meijer K, Hamulyak K, Nijziel MR, Fijnvandraat K, Leebeek FW; WiN study group. Determinants of bleeding phenotype in adult patients with moderate or severe von Willebrand disease. Thromb Haemost. 2012 Oct;108(4):683-92. doi: 10.1160/TH12-04-0244. Epub 2012 Aug 23.
citation: van Galen KPM, de Kleijn P, Foppen W, Eikenboom J, Meijer K, Schutgens REG, Fischer K, Cnossen MH, de Meris J, Fijnvandraat K, van der Bom JG, Laros-van Gorkom BAP, Leebeek FWG, Mauser-Bunschoten EP; Win study group. Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study. Haematologica. 2017 Sep;102(9):1486-1493. doi: 10.3324/haematol.2017.168617. Epub 2017 Jun 1.
citation: Sanders YV, Fijnvandraat K, Boender J, Mauser-Bunschoten EP, van der Bom JG, de Meris J, Smiers FJ, Granzen B, Brons P, Tamminga RY, Cnossen MH, Leebeek FW; WiN Study Group. Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding. Am J Hematol. 2015 Dec;90(12):1142-8. doi: 10.1002/ajh.24195. Epub 2015 Nov 17.
citation: van Galen KPM, Meijer K, Vogely HC, Eikenboom J, Schutgens REG, Cnossen MH, Fijnvandraat K, van der Bom JG, Laros-van Gorkom BAP, Leebeek FWG, Mauser-Bunschoten EP; WiN study group. Joint surgery in von Willebrand disease: a multicentre cross-sectional study. Haemophilia. 2016 Mar;22(2):256-262. doi: 10.1111/hae.12834. Epub 2015 Nov 9.
citation: Atiq F, Meijer K, Eikenboom J, Fijnvandraat K, Mauser-Bunschoten EP, van Galen KPM, Nijziel MR, Ypma PF, de Meris J, Laros-van Gorkom BAP, van der Bom JG, de Maat MP, Cnossen MH, Leebeek FWG; WiN study group. Comorbidities associated with higher von Willebrand factor (VWF) levels may explain the age-related increase of VWF in von Willebrand disease. Br J Haematol. 2018 Jul;182(1):93-105. doi: 10.1111/bjh.15277. Epub 2018 May 16.