Rare Bleeding DisordersRBINNCT03347591
Rare Bleeding Disorders in the Netherlands
An observational study of Rare Bleeding Disorders, run by Radboud University Medical Center at 7 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Rare Bleeding Disorders
- What is being tested?
- WES and Several assays
- How many people
- 300 participants
- Where
- 7 sitesNetherlands
- Study dates
- 7 Nov 2017to 1 Jan 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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).
Who cannot join
- No informed consent given;
- Residency outside of the Netherlands
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Netherlands7 sites, 7 recruiting
- Recruiting
Academisch Medisch Centrum
Amsterdam
Marjolein Peters, Dr., m.peters@amc.uva.nl
- Recruiting
Maxima Medisch Centrum
Eindhoven, 6500 PD
Laurens Nieuwenhuizen, PhD
- Recruiting
University Medical Center Groningen (UMCG)
Groningen
Vellenga, Prof MD PhD, +31 (0)50 3613385, hematologiestudie@umcg.nl
Vellenga, Prof MD PhD
- Recruiting
Maatricht UMC+
Maastricht, 6202 AZ
Erik Beckers, Dr., eam.beckers@mumc.nl
- Recruiting
Radboud university medical center
Nijmegen, 6525 GA
Postbus Trialbureau Hematologie-Oncologie, +31 24 36 14 794, trialbureauhemat-onco@radboudumc.nl
S. Schols, MD PhD
- Recruiting
Erasmus MC
Rotterdam, 3000CA
Marjon Cnossen, m.cnossen@erasmusumc.nl
- Recruiting
Haga hospital
The Hague, 2545AA
Paul Ypma, P.Ypma@hagaziekenhuis.nl
About this study
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.
Read more
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.
Read the 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
- Conditions
- Rare Bleeding Disorders
- Being tested
- WES, Several assays
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WESGenetic
136 bleeding related OMIM (Online Mendelian Inheritance in Man)-proved genes involved in haemostasis will be selected from Whole Exome Sequencing (WES)
Several assaysDiagnostic test
Also called Hemostasis (several screening tests, several diagnostic tests, global assay), Fibrinolysis, Lupus anticoagulans, Anti β2 glycoprotein
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: WES; Diagnostic Test: Several assays |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epidemiology
Determine the prevalence of rare bleeding disorders in the Netherlands by evaluating all patients known in all Dutch Haemophilia Treatment Centers
Measured: 1 year
Phenotype
Clinical phenotype will be measured by bleeding scores measured as ISTH-BAT.
Measured: 1 year
Laboratory phenotype
Measure the factor concentrations of all patients known with a Rare Bleeding Disorder in the Netherlands
Measured: 1 year
Quality of Life
Quality of life will be measured using the RAND-36 questionnaire
Measured: 2 years
Genotype
Determine the genotype of patients (homozygous, heterozygous, compound heterozygous) by whole exome sequencing
Measured: 2 years
Secondary outcomes (2)
Minimum factor level
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
Measured: 1 year
Age
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.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2017
- Study start7 Nov 2017
- Primary completion1 Jul 2021 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rare Bleeding DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Academisch Ziekenhuis Maastricht, Erasmus Medical Center, Maxima Medical Center, Academisch Ziekenhuis Groningen, UMC Utrecht, Leiden University Medical Center, Haga Hospital
- Responsible party
- Sponsor
- Investigators
- S. Schols, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03347591
- Sponsor's protocol ID
- HEMSTOL47
- Acronym
- RBIN
- Status last verified
- Jan 2021
- First submitted
- 25 Oct 2017
- Last updated
- 15 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided
Publications
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.
PubMed 33064819
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rare Bleeding Disorders in the Netherlands
- ClinicalTrials.gov ID
- NCT03347591
- Acronym / sponsor ID
- RBIN / HEMSTOL47
- Conditions
- Rare Bleeding Disorders
- Keywords
- Fibrinogen, Factor II, Factor V, Factor V & VIII, Factor VII, Factor X, Factor XI, Factor XIII
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Academisch Ziekenhuis Maastricht, Erasmus Medical Center, Maxima Medical Center, Academisch Ziekenhuis Groningen, UMC Utrecht, Leiden University Medical Center, Haga Hospital
- Study start
- 7 Nov 2017 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 20 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with rare bleeding disorders | – | Genetic: WES, Diagnostic Test: Several assaysAll 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. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (2 listed)
- No informed consent given;
- Residency outside of the Netherlands
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WES136 bleeding related OMIM (Online Mendelian Inheritance in Man)-proved genes involved in haemostasis will be selected from Whole Exome Sequencing (WES) | Genetic | Patients with rare bleeding disorders |
| Several assaysAlso: Hemostasis (several screening tests, several diagnostic tests, global assay), Fibrinolysis, Lupus anticoagulans, Anti β2 glycoproteinPatients 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. | Diagnostic test | Patients with rare bleeding disorders |
Primary outcome
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
Phenotype
Time frame: 1 year
Clinical phenotype will be measured by bleeding scores measured as ISTH-BAT.
Laboratory phenotype
Time frame: 1 year
Measure the factor concentrations of all patients known with a Rare Bleeding Disorder in the Netherlands
Quality of Life
Time frame: 2 years
Quality of life will be measured using the RAND-36 questionnaire
Genotype
Time frame: 2 years
Determine the genotype of patients (homozygous, heterozygous, compound heterozygous) by whole exome sequencing
2 secondary outcomes
Minimum factor level
Time frame: 1 year
Age
Time frame: 1 Year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2021.
- Derived from this study: PubMed 33064819Saes 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.
- Individual participant dataSharing planned: Undecided. Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
S. Schols, PhD principal investigator
Radboud University Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rare Bleeding Disorders, run by Radboud University Medical Center at 7 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact J. Saes, Drs. (0031243614794, Joline.Saes@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epidemiology (time frame: 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03347591, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2021.