Von Willebrand Disease in the Netherlands

Von Willebrand Disease Clinical Trial

— WiN-Pro  

Official title:

Von Willebrand Disease in the Netherlands - Prospective Study (WiN-Pro)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03521583
• Other study ID #: NL62238.078.18
• Status: Recruiting
• Start date: July 28, 2019
• Est. completion date: January 2022

Study information

• Verified date: August 2020
• Source: Erasmus Medical Center
• Contact: Frank WG Leebeek, MD, PhD
• Phone: +31107031369
• Email: f.leebeek[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: January 2022
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Von Willebrand Disease
• Von Willebrand Diseases

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Haga Hospital	Den Haag
Netherlands	Maxima Medical Center	Eindhoven
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 University Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (4)

Lead Sponsor	Collaborator
Erasmus Medical Center	CSL Behring, Shire, Stichting Haemophilia (Dutch Haemophilia Foundation)

Country where clinical trial is conducted

Netherlands, 

References & Publications (8)

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. — View 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. — View 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, Hamulyák 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. Epub 2012 Aug 23. — View Citation

Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med. 2016 Nov 24;375(21):2067-2080. Review. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bleeding rate	Number of bleedings in an individual divided by the follow-up duration	2 years