Rare Bleeding Disorders in the Netherlands

NCT ID: NCT03347591

Last Updated: 2021-01-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-11-07

Study Completion Date

2022-01-01

Brief Summary

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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.

Detailed Description

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Primary objectives:

* Describe the epidemiology, clinical presentation, bleeding score, bleeding episodes, quality of life, laboratory parameters, genetics and treatment of homozygous and known heterozygous individuals (of all ages) with rare bleeding disorders (disorders of fibrinogen, FII, FV, FV \& VIII, FVII, FX, FXI, FXIII, alpha-2-antiplasmin and PAI-1 deficiency) in the Netherlands;
* Examine the relationship between the clinical and laboratory presentation (clinical and laboratory phenotype), and between phenotypes and genetics (genotype);
* Examine the relationship between quality of life, phenotype and genotype;
* Validate the established factor activity levels for patients to remain without symptoms.

Secondary objectives:

* Compare the clinical presentation, bleeding score, quality of life and laboratory parameters of individuals with a rare bleeding disorder (disorders of fibrinogen, FII, FV, FV \& VIII, FVII, FX, FXI, FXIII, alpha-2-antiplasmin and PAI-1 deficiency) to those of individuals with haemophilia A or B in cooperation with the HIN-6 investigators
* Establish a firm base for a future Dutch registry for homozygous and known heterozygous individuals with rare bleeding disorders
* To develop a standard set of patient-reported, clinical and administrative data to be collected on a regular basis
* Liaise with the pro-RBDD study, a similar study in Italy, to work towards a pan-European study linking phenotype to genotype in individuals with rare bleeding disorders
* To assess if the NHA can distinguish mild clinical phenotypes in patients with similar factor activity levels
* To evaluate the usefulness of saliva coagulation biomarker tests in the management of patients with a rare bleeding disorder
* To examine whether age-dependent laboratory changes in factor concentrations and fibrinolysis occur in individuals with rare bleeding disorders and if so, whether they influence clinical phenotype
* To evaluate if patients with rare bleeding disorders are protected from arterial thrombosis

Conditions

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Rare Bleeding Disorders

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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.

WES

Intervention Type GENETIC

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

Several assays

Intervention Type 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.

Interventions

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WES

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

Intervention Type GENETIC

Several assays

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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* No informed consent given;
* Residency outside of the Netherlands
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role collaborator

Academisch Ziekenhuis Maastricht

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Maxima Medical Center

OTHER

Sponsor Role collaborator

Academisch Ziekenhuis Groningen

OTHER

Sponsor Role collaborator

UMC Utrecht

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

Haga Hospital

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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S. Schols, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Academisch Medisch Centrum

Amsterdam, , Netherlands

Site Status RECRUITING

Maxima Medisch Centrum

Eindhoven, , Netherlands

Site Status RECRUITING

University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Site Status RECRUITING

Maatricht UMC+

Maastricht, , Netherlands

Site Status RECRUITING

Radboud university medical center

Nijmegen, , Netherlands

Site Status RECRUITING

Erasmus MC

Rotterdam, , Netherlands

Site Status RECRUITING

Haga hospital

The Hague, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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J. Saes, Drs.

Role: CONTACT

0031243614794

Facility Contacts

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Marjolein Peters, Dr.

Role: primary

Laurens Nieuwenhuizen, PhD

Role: primary

Vellenga, Prof MD PhD

Role: primary

+31 (0)50 3613385

Erik Beckers, Dr.

Role: primary

Postbus Trialbureau Hematologie-Oncologie

Role: primary

+31 24 36 14 794

Marjon Cnossen

Role: primary

Paul Ypma

Role: primary

References

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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.

Reference Type DERIVED
PMID: 33064819 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HEMSTOL47

Identifier Type: -

Identifier Source: org_study_id

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