Clinical trial NCT02869074: Molecular and Clinical Profile of Von Willebrand Disease in Spain
Official title: Molecular and Clinical Profile of Von Willebrand Disease (VWD) in Spain (PCM-EVW-ES). Recruitment Extension, Further Data Analysis, Improvement of Registry Platform, Diagnosis and Management of VWD Application Development
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Von Willebrand Disease
Keywords: von Willebrand disease (VWD)
von Willebrand factor (VWF)
von Willebrand factor gene
next generation sequencing
diagnosis
VWD Spanish Cohort
Lead sponsor: Spanish Society of Thrombosis and Haemostasis
Sponsor class: OTHER
Collaborators: name: Francisco Vidal Pérez
name: Maria Fernanda López Fernández
name: Almudena Pérez Rodríguez
name: Irene Corrales Insa
name: Ana Rosa Cid Haro
First posted: 2016-08-16
Enrollment: 790
Sex: ALL
Minimum age (years): 2
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Up to 676 new patients (not previously recruited for the Spanish Registry) locally diagnosed of VWD.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Central diagnosis of 400 new VWD Spanish patients
timeFrame: January 2019
Secondary outcomes:
measure: PCM-EVW-ES project algorithm validation/confirmation
timeFrame: January 2019
measure: Potential collaboration with the International Society on Thrombosis and Haemostasis
timeFrame: January 2019
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
Study officials:
affiliation: Complexo Hospitalario Universitario A Coruña. INIBIC. A Coruña. Spain
name: Francisco Javier BATLLE, PhD, MD
role: STUDY_CHAIR
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citation: Borras N, Garcia-Martinez I, Batlle J, Perez-Rodriguez A, Parra R, Altisent C, Lopez-Fernandez MF, Costa Pinto J, Batlle-Lopez F, Cid AR, Bonanad S, Cabrera N, Moret A, Mingot-Castellano ME, Navarro N, Perez-Montes R, Marcellini S, Moreto A, Herrero S, Soto I, Fernandez-Mosteirin N, Jimenez-Yuste V, Alonso N, de Andres-Jacob A, Fontanes E, Campos R, Paloma MJ, Bermejo N, Berrueco R, Mateo J, Arribalzaga K, Marco P, Palomo A, Castro Quismondo N, Inigo B, Del Mar Nieto M, Vidal R, Martinez MP, Aguinaco R, Tenorio M, Ferreiro M, Garcia-Frade J, Rodriguez-Huerta AM, Cuesta J, Rodriguez-Gonzalez R, Garcia-Candel F, Dobon M, Aguilar C, Corrales I, Vidal F. Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort. Thromb Haemost. 2020 Mar;120(3):437-448. doi: 10.1055/s-0040-1702227. Epub 2020 Mar 5.