Rare Bleeding Disorders in the Netherlands

NCT03347591 | Unknown

• 1 other identifier: HEMSTOL47
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 7

Brief Summary

Rationale: Rare bleeding disorders (deficiency of fibrinogen, factor II, V, V\&VIII, VII, X, XI, XIII, α2-antiplasmin or plasminogen activator inhibitor 1) are not well defined with respect to their clinical phenotype, laboratory phenotype en genotype. At present, little is known about their clinical presentation, bleeding scores, bleeding episodes, health-related quality of life, laboratory parameters, genetics and current treatment. There are large differences in bleeding tendency and weak correlations with the level of factor deficiencies. Therefore, it is essential to perform thorough research in patients with rare bleeding disorders and perform laboratory and genetic tests, to seek explanations for the variety in clinical phenotype. Objective: The purpose of the RBIN study is to describe the epidemiology, bleeding tendency, laboratory parameters, quality of life and genetics of all known patients in the Netherlands with rare bleeding disorders. In addition, the study aims to examine the relationship between clinical phenotype, laboratory phenotype and genotype. Study design: explorative cross-sectional multicenter observational study Study population: all patients registered in Dutch Haemophilia Treatment Centers with known disorders of the coagulation factors fibrinogen, factor II, V, V \& VIII, VII, X, XI, XIII, α2-antiplasmin and plasminogen activator inhibitor type 1, aged 1 years and older. Main study parameters/endpoints: Description of the clinical phenotype, laboratory phenotype, genotype and quality of life. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: participating patients will be invited for one visit to their treatment center in order to draw blood, take a saliva sample and perform questionnaires. This will take approximately 40 to 120 minutes. Since the population of patients with rare bleeding disorders is very small it is important to include all patients, also minors (children \<18 years), in the study (around one third of known patients are minors). Therefore, this study may be regarded as group-related. The risk associated with participation is negligible.

Conditions

Rare Bleeding Disorders

Keywords

Fibrinogen; Factor II; Factor V; Factor V & VIII; Factor VII; Factor X; Factor XI; Factor XIII; α2-antiplasmin; Plasminogen activator inhibitor 1; Epidemiology; Genetics; Phenotype

Outcome Measures

Primary Outcomes (5)

• Epidemiology

  Determine the prevalence of rare bleeding disorders in the Netherlands by evaluating all patients known in all Dutch Haemophilia Treatment Centers

  1 year

• Phenotype

  Clinical phenotype will be measured by bleeding scores measured as ISTH-BAT.

  1 year

• Laboratory phenotype

  Measure the factor concentrations of all patients known with a Rare Bleeding Disorder in the Netherlands

  1 year

• Quality of Life

  Quality of life will be measured using the RAND-36 questionnaire

  2 years

• Genotype

  Determine the genotype of patients (homozygous, heterozygous, compound heterozygous) by whole exome sequencing

  2 years

Secondary Outcomes (2)

• Minimum factor level

  1 year

• Age

  1 Year

Study Arms (1)

Patients with rare bleeding disorders

All patients registered in Dutch Haemophilia Treatment Centers with known disorders of the coagulation factors fibrinogen, factor II, V, V \& VIII, VII, X, XI, XIII, α2-antiplasmin and plasminogen activator inhibitor type 1, aged 1 years and older.

Genetic: WES; Diagnostic Test: Several assays

Interventions

WES GENETIC

136 bleeding related OMIM (Online Mendelian Inheritance in Man)-proved genes involved in haemostasis will be selected from Whole Exome Sequencing (WES)

Patients with rare bleeding disorders

Several assays DIAGNOSTIC_TEST

Patients will be approached by their own treating physician. Data will be collected through questionnaires, a clinical interview, a blood and saliva sample obtained from each participant, and thorough review of electronic patient records. All procedures are study related. In case a physician visit with the treating physician is already planned, or in case a venepuncture for regular diagnostics or treatment is already planned, this can be combined with the study procedures to prevent an extra visit.

Also known as: Hemostasis (several screening tests, several diagnostic tests, global assay), Fibrinolysis, Lupus anticoagulans, Anti β2 glycoprotein

Patients with rare bleeding disorders

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

To date, 394 patients with a rare bleeding disorder are known to the eight Dutch centers that treat such patients. Approximately one third of these patients are homozygous; and around two thirds are heterozygous individuals. All known homozygous and heterozygous patients with a rare bleeding disorder will be invited to participate.

You may qualify if:

• Established homozygous or known heterozygous rare bleeding disorder due to deficiency or dysfunction of fibrin, FII, FV, FV \& FVIII, FVII, FX, FXI, FXIII, alpha-2-antiplasmin and PAI-1 ;
• Age 1 year and older;
• For patients ≥ 16 years old; written informed consent.
• For patients 12-16 years old; written informed consent from both the patient and their parents/legal guardian(s).
• For patients \<12 years old; written informed consent from their parents/legal guardian(s).

You may not qualify if:

• No informed consent given;
• Residency outside of the Netherlands

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Academisch Ziekenhuis Maastricht: collaborator
• Erasmus Medical Center: collaborator
• Maxima Medical Center: collaborator
• Academisch Ziekenhuis Groningen: collaborator
• UMC Utrecht: collaborator
• Leiden University Medical Center: collaborator
• Haga Hospital: collaborator

Study Sites (7)

Academisch Medisch Centrum

Amsterdam, Netherlands

RECRUITING

Maxima Medisch Centrum

Eindhoven, 6500 PD, Netherlands

RECRUITING

University Medical Center Groningen (UMCG)

Groningen, Netherlands

RECRUITING

Maatricht UMC+

Maastricht, 6202 AZ, Netherlands

RECRUITING

Radboud university medical center

Nijmegen, 6525 GA, Netherlands

RECRUITING

Erasmus MC

Rotterdam, 3000CA, Netherlands

RECRUITING

Haga hospital

The Hague, 2545AA, Netherlands

RECRUITING

Related Publications (1)

• Saes JL, Verhagen MJA, Meijer K, Cnossen MH, Schutgens REG, Peters M, Nieuwenhuizen L, van der Meer FJM, Kruis IC, van Heerde WL, Schols SEM. Bleeding severity in patients with rare bleeding disorders: real-life data from the RBiN study. Blood Adv. 2020 Oct 27;4(20):5025-5034. doi: 10.1182/bloodadvances.2020002740.

  PMID: 33064819 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood and saliva

MeSH Terms

Interventions

Hemostasis; Fibrinolysis

Intervention Hierarchy (Ancestors)

Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Blood Coagulation

Study Officials

• S. Schols, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

J. Saes, Drs.

CONTACT

0031243614794; Joline.Saes@radboudumc.nl

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: November 20, 2017
• Study Start: November 7, 2017
• Primary Completion: July 1, 2021
• Study Completion: January 1, 2022
• Last Updated: January 15, 2021

Record last verified: 2021-01

Locations

NL (7)