Rare Bleeding Disorders in the Netherlands (RBIN)

January 14, 2021 updated by: Radboud University Medical Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Academisch Medisch Centrum
        • Contact:
      • Den Haag, Netherlands, 2545AA
      • Eindhoven, Netherlands, 6500 PD
        • Recruiting
        • Maxima Medisch Centrum
        • Contact:
          • Laurens Nieuwenhuizen, PhD
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen (UMCG)
        • Contact:
        • Principal Investigator:
          • Vellenga, Prof MD PhD
      • Maastricht, Netherlands, 6202 AZ
      • Nijmegen, Netherlands, 6525 GA
        • Recruiting
        • Radboud University Medical Center
        • Contact:
        • Principal Investigator:
          • S. Schols, MD PhD
      • Rotterdam, Netherlands, 3000CA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
136 bleeding related OMIM (Online Mendelian Inheritance in Man)-proved genes involved in haemostasis will be selected from Whole Exome Sequencing (WES)
Diagnostic test: 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.
Other Names:
  • Hemostasis (several screening tests, several diagnostic tests, global assay)
  • Fibrinolysis
  • Lupus anticoagulans
  • Anti β2 glycoprotein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epidemiology
Time Frame: 1 year
Determine the prevalence of rare bleeding disorders in the Netherlands by evaluating all patients known in all Dutch Haemophilia Treatment Centers
1 year
Phenotype
Time Frame: 1 year
Clinical phenotype will be measured by bleeding scores measured as ISTH-BAT.
1 year
Laboratory phenotype
Time Frame: 1 year
Measure the factor concentrations of all patients known with a Rare Bleeding Disorder in the Netherlands
1 year
Quality of Life
Time Frame: 2 years
Quality of life will be measured using the RAND-36 questionnaire
2 years
Genotype
Time Frame: 2 years
Determine the genotype of patients (homozygous, heterozygous, compound heterozygous) by whole exome sequencing
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum factor level
Time Frame: 1 year
The minimum factor level necessary to remain without bleeding will be calculated by measuring factor levels in all patients and their bleeding scores by ISTH-BAT
1 year
Age
Time Frame: 1 Year
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.
1 Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

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

Investigators

  • Principal Investigator: S. Schols, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 7, 2017

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

January 1, 2022

Study Registration Dates

First Submitted

October 25, 2017

First Submitted That Met QC Criteria

November 15, 2017

First Posted (Actual)

November 20, 2017

Study Record Updates

Last Update Posted (Actual)

January 15, 2021

Last Update Submitted That Met QC Criteria

January 14, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HEMSTOL47

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rare Bleeding Disorders

Clinical Trials on WES

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe