Molecular and Clinical Profile of Von Willebrand Disease in Spain

Completed

• Conditions: Von Willebrand Disease
• Interventions: Genetic: VWF gene analysis

• Registration Number: NCT02869074
• Lead Sponsor: Spanish Society of Thrombosis and Haemostasis

Brief Summary

The present Project is a third phase of the previous PCM-EVW-ES Project (Batlle et al. Thromb \& Haemost 2015) with the aim of its extension, further analysis with an innovation development in the field of von Willebrand disease (VWD) based in the newer recently available methodologies. The aim of this project is to help the physician in a more uniform characterization and therapy of VWD in clinical practice, at an international level. A reduction of the expenses in the diagnosis process by using the new methodologies is pursued.

Detailed Description

The present Project is a third phase of the previous PCM-EVW-ES Project (Batlle et al. Thromb \& Haemost 2015) with the aim of its extension, further analysis with an innovation development in the field of von Willebrand disease (VWD) based in the newer recently available methodologies. The aim of this project is to help the physician in a more uniform characterization and therapy of VWD in clinical practice, at an international level. A reduction of the expenses in the diagnosis process by using the new methodologies is pursued.

The specific objectives and corresponding tasks of the present project are as follows:

1. Extension of the central phenotypic and next generation sequencing (NGS) genotypic characterization of the VWD in Spain, through the prospective recruitment in the Spanish VWD cohort of approximately 500 new patients with local historical VWD diagnosis (from approximately 38 centres).

i. Improvement of the registry portal and database. ii. Recruitment criteria, phenotypic and genetic analysis of new recruited patients. In silico studies of novel von Willebrand factor gene (VWF) mutations iii. Analysis/investigation of the potential interrelationship between different clinical, phenotypic and genetic variations of the all recruited patients. iv. Validation/confirmation of the PCM-EVW-ES of the new initial diagnostic proposed algorithm including VWF NGS analysis. This project involves leading innovation and translational research with a direct impact on the quality of clinical care (applicability). To our knowledge there is no similar project in this field. Potential patents may derive from this project. It involves also development of e-learning and new information technologies (debates forum, ads, google search engine). This project may promote international collaboration.

Development of an algorithmic platform that facilitates diagnosis and therapy orientation of VWD in clinical practice using the selected data from the overwhelming amount of information that new technologies, such as NGS, are producing.

Study Timeline

• Study First Submitted: 2016-07-29
• Study First Submitted QC: 2016-08-11
• Study First Posted: 2016-08-16
• Study Start: 2017-10-03
• Primary Completion: 2021-09-25
• Study Completion: 2021-09-25
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 790

Inclusion Criteria

One or more of the following:

1. VWF ≤ 30 IU/d, in 2 or more occasions.
2. Presence of multimeric abnormalities.
3. If isolated FVIII deficiency demonstration of decreased FVIII binding.
4. Presence of some VWF mutation.
5. ↑ RIPA at low concentrations of ristocetin.

Exclusion Criteria

1. Presence of any data suggesting AVWS.
2. Absence of a signed patient informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
VWD Spanish Cohort	VWF gene analysis	Patients with previously diadnosis of VWD from approximately 38-40 different centers from Spain. Samples from these patients will be analyzed locally, and also centrally for VWF and VWFgene

Primary Outcome Measures

Name	Time	Method
Central diagnosis of 400 new VWD Spanish patients	January 2019	Phenotype and genetic central diagnosis of 400 new VWD Spanish patients. With determinations in samples obtained after patients recruitment, VWF NGS sequencing carried out in all patients, for exons 1 to 52, adjacent intronic regions and aproximately 1300 bp of promotor region.; A pheno-genotype will be made With a final diagnosis assignment Evaluation of pheno/genotype congruence

Secondary Outcome Measures

Name	Time	Method
Potential collaboration with the International Society on Thrombosis and Haemostasis	January 2019	Proposal for evaluation of the PCM-EVW-ES algorithm with data from other international VWD patients cohorts
PCM-EVW-ES project algorithm validation/confirmation	January 2019	Evaluation of the algorithm with data from the Spanish Registry patients. Mutation results will be used in the first line of VWD diagnosis Correlation between mutations and phenotype

Trial Locations

Locations (1)

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain