Haemophilia2BEGINNCT06809972
Synovial Proliferation on Routine Ultrasound: Active or Inactive?
An observational study of Haemophilia and Hemophilia A, run by Van Creveldkliniek at 1 site in Netherlands.
Trial summary
There is cumulating evidence for the presence of non-observed or subclinical joint bleeding in patients with haemophilia. Early detection of active subclinical synovial proliferation would allow early intervention in order to prevent deterioration of joint health. Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- Haemophilia, Hemophilia A, Hemophilia B
- What is being tested?
- Ultrasound imaging
- How many people
- 46 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jun 2025to 1 Apr 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population consists of male participants ≥ 12 years of age, with severe haemophilia A or B treated with prophylaxis, who were diagnosed with asymptomatic synovial proliferation in ≥1 joint (ankle, knee and/or elbow) by means of ultrasound imaging during routine screening at the outpatient clinic of the Van Creveldkliniek, UMC Utrecht, the Netherlands.
Who may be able to join
- Gender: male
- Patients with severe haemophilia A or B
- Treated with registered prophylaxis medication including coagulation factors and by- passing agents.
- Age ≥ 12 years
- Subclinical synovial proliferation in ≥1 joint (ankle, knee and/or elbow), defined as the presence of hypertrophic synovium, score >0 according to the HEAD-US protocol, as confirmed during routine ultrasound screening.
- Able to give written informed consent.
Who cannot join
- A major bleed ≤ 3 months or a minor bleed ≤ 1 month prior to inclusion in the joint of interest.
- On demand therapy.
- Currently treated with any type of haemophilia prophylaxis medication.
- Joints with prosthesis or treated with arthrodesis will not be included for physical examination and ultrasound analysis. However, participants may still be included in the study with their other joints.
- Confirmed inflammatory joint diseases such as rheumatoid arthritis or psoriatic arthritis.
- History of inhibitor development (≥ 5 Bethesda Units* (BU) at any time or 1-5 BU for
- 1 year prior to inclusion.
- Contra-indication for treatment with NSAIDs, (allergy, severe liver failure, renal failure (GFR <30ml/min), congestive heart failure (NYHA II-IV), peripheral arterial disease and/or cerebrovascular disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Merel Timmer, PhD contact
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Utrecht
Utrecht, 3584CX
Lize van, MD, PhD, +31887558450, l.f.d.vanvulpen-2@umcutrecht.nl
Merel Timmer, PhD
About this study
Official title: Synovial Proliferation on Routine Ultrasound: Active or Inactive? A Prospective Study
There is cumulating evidence for the presence of non-observed or subclinical joint bleeding in patients with haemophilia. Early detection of active subclinical synovial proliferation would allow early intervention in order to prevent deterioration of joint health. Patients with subclinical (=non-observed) signs of synovial proliferation in knee(s), ankle(s) and/or elbow(s) will be invited to participate in this study to further characterize the synovial proliferation status (active or inactive) by means of physical examination, MRI, ultrasound and elastography. Synovial proliferation status will be monitored for a maximum period of 12 weeks, during which participants will also receive standard-of-care treatment, i.e. administration of optimized coagulation factor replacement therapy and prescription of the NSAID celecoxib (optional).
Read the detailed description
To be completed
- Conditions
- Haemophilia, Hemophilia A, Hemophilia B
- Being tested
- Ultrasound imaging
- Keywords
- Subclinical synovial proliferation, Ultrasound, MRI, Elastography
- Medical subject headings
- Hemophilia A, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound imagingOther
Also called MRI, Elastography
Ultrasound, MRI and elastography to screen for and follow subclinical synovial changes in ankle, elbow and knee.
What is being measured
The primary outcome is the main question the study is designed to answer.
- The primary objective of this study is to evaluate the diagnostic accuracy of physical examination and ultrasound to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy.
As no gold standard to identify active subclinical proliferation is available, "change in synovial proliferation over time" will be used as surrogate endpoint. This is measured by ultrasound assessment according HEAD-US protocol . Possible outcomes are: no change (baseline HEAD-US score = 12-week follow-up HEAD-US score) or changed (baseline HEAD-US score < or > 12-week follow-up HEAD-US score). Fully recovered synovial proliferation will also be categorized as changed. The diagnostic accuracy will be derived comparing 'change in synovial proliferation' with the 'presumed' definition at baseline (active or inactive).
Definition of active synovial proliferation at baseline: synovial proliferation on ultrasound and the presence of at least one of the following criteria:
- HJHS swelling >0
- Warmth palpation absent/present at baseline
- JADE Synovial Hyperaemia >0
- No history of synovial proliferation (yes/no)
- Hemosiderin on MRI (IPSG>0)
- Elastography
Measured: 12 weeks
Secondary outcomes (3)
- To identify predictors for (changes in) synovial proliferation status within participant characteristics (age, baseline treatment, joint bleeding history) and joint characteristics (extent of arthropathy (Pettersson score on X-rays)).
Baseline participant characteristics (age, baseline treatment, joint bleeding history) and joint characteristics (extent of arthropathy (Pettersson score on X-rays)) will be extracted from medical files.
Measured: 12 weeks
- To evaluate the diagnostic accuracy of the presence of synovial hemosiderin, as measured by MRI, to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy.
Clinical and ultrasound definition of active synovial proliferation: synovial proliferation on ultrasound (HEAD-US synovium score >0) and the presence of at least one of the following criteria:
- Hemosiderin on MRI: IPSG score Hemosiderin Deposit > 0 at baseline
Measured: 12 weeks
- To evaluate the diagnostic accuracy of synovial elastography to identify active synovial proliferation in hemophilia patients with subclinical synovial hypertrophy
Clinical and ultrasound definition of active synovial proliferation: synovial proliferation on ultrasound (HEAD-US synovium score >0) and the presence of at least one of the following criteria:
- Elastography:
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start1 Jun 2025
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HaemophiliaStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Van Creveldkliniek
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Van Creveldkliniek, UMC Utrecht
- Investigators
- Lize van Vulpen, MD, PhD, Principal investigator, University Medical Center Utrecht - Van Creveldkliniek
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06809972
- Sponsor's protocol ID
- 2BEGIN
- Acronym
- 2BEGIN
- Status last verified
- Apr 2026
- First submitted
- 30 Oct 2024
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pseudonimyzed data may be shared with other (international) researchers upon request at the principal investigator. On group level, data will be presented at congresses and in peer-reviewed articles.
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synovial Proliferation on Routine Ultrasound: Active or Inactive? A Prospective Study
- ClinicalTrials.gov ID
- NCT06809972
- Acronym / sponsor ID
- 2BEGIN / 2BEGIN
- Conditions
- Haemophilia, Hemophilia A, Hemophilia B
- Keywords
- Subclinical synovial proliferation, Ultrasound, MRI, Elastography
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Van CreveldkliniekUniversity, hospital or other
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 5 Feb 2025 (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.
There is cumulating evidence for the presence of non-observed or subclinical joint bleeding in patients with haemophilia. Early detection of active subclinical synovial proliferation would allow early intervention in order to prevent deterioration of joint health. Patients with subclinical (=non-observed) signs of synovial proliferation in knee(s), ankle(s) and/or elbow(s) will be invited to participate in this study to further characterize the synovial proliferation status (active or inactive) by means of physical examination, MRI, ultrasound and elastography. Synovial proliferation status will be monitored for a maximum period of 12 weeks, during which participants will also receive standard-of-care treatment, i.e. administration of optimized coagulation factor replacement therapy and prescription of the NSAID celecoxib (optional).
Detailed description
To be completed
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population consists of male participants ≥ 12 years of age, with severe haemophilia A or B treated with prophylaxis, who were diagnosed with asymptomatic synovial proliferation in ≥1 joint (ankle, knee and/or elbow) by means of ultrasound imaging during routine screening at the outpatient clinic of the Van Creveldkliniek, UMC Utrecht, the Netherlands.
Key inclusion criteria (6 listed)
- Gender: male
- Patients with severe haemophilia A or B
- Treated with registered prophylaxis medication including coagulation factors and by- passing agents.
- Age ≥ 12 years
- Subclinical synovial proliferation in ≥1 joint (ankle, knee and/or elbow), defined as the presence of hypertrophic synovium, score >0 according to the HEAD-US protocol, as confirmed during routine ultrasound screening.
Key exclusion criteria (8 listed)
- A major bleed ≤ 3 months or a minor bleed ≤ 1 month prior to inclusion in the joint of interest.
- On demand therapy.
- Currently treated with any type of haemophilia prophylaxis medication.
- Joints with prosthesis or treated with arthrodesis will not be included for physical examination and ultrasound analysis. However, participants may still be included in the study with their other joints.
- Confirmed inflammatory joint diseases such as rheumatoid arthritis or psoriatic arthritis.
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 |
|---|---|---|
| Ultrasound imagingAlso: MRI, ElastographyUltrasound, MRI and elastography to screen for and follow subclinical synovial changes in ankle, elbow and knee. | Other | – |
Primary outcome
- The primary objective of this study is to evaluate the diagnostic accuracy of physical examination and ultrasound to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy.
Time frame: 12 weeks
As no gold standard to identify active subclinical proliferation is available, "change in synovial proliferation over time" will be used as surrogate endpoint. This is measured by ultrasound assessment according HEAD-US protocol . Possible outcomes are: no change (baseline HEAD-US score = 12-week follow-up HEAD-US score) or changed (baseline HEAD-US score < or > 12-week follow-up HEAD-US score). Fully recovered synovial proliferation will also be categorized as changed. The diagnostic accuracy will be derived comparing 'change in synovial proliferation' with the 'presumed' definition at baseline (active or inactive). Definition of active synovial proliferation at baseline: synovial proliferation on ultrasound and the presence of at least one of the following criteria: * HJHS swelling >0 * Warmth palpation absent/present at baseline * JADE Synovial Hyperaemia >0 * No history of synovial proliferation (yes/no) * Hemosiderin on MRI (IPSG>0) * Elastography
3 secondary outcomes
- To identify predictors for (changes in) synovial proliferation status within participant characteristics (age, baseline treatment, joint bleeding history) and joint characteristics (extent of arthropathy (Pettersson score on X-rays)).
Time frame: 12 weeks
- To evaluate the diagnostic accuracy of the presence of synovial hemosiderin, as measured by MRI, to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy.
Time frame: 12 weeks
- To evaluate the diagnostic accuracy of synovial elastography to identify active synovial proliferation in hemophilia patients with subclinical synovial hypertrophy
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Individual participant dataSharing planned: Yes. Pseudonimyzed data may be shared with other (international) researchers upon request at the principal investigator. On group level, data will be presented at congresses and in peer-reviewed articles.
Related trials for Haemophilia
Active, not recruitingPhase 3
Study to Provide Continued Access to Treatment for Patients Completing a Previous Trial With Efanesoctocog Alfa
Haemophilia A (Moderate or Severe)
Enrolling by invitationObservational study
Adverse Event Data Collection From External Registries on Nonacog Beta Pegol
Haemophilia B
Enrolling by invitationObservational study
Adverse Event Data Collection From the EUHASS Registry on Turoctocog Alfa Pegol
Haemophilia A
RecruitingObservational study
Determinants and Consequences of the Transition to Adulthood for Adolescents With Severe Haemophilia: TRANSHEMO 2, an Ancillary Study to the TRANSHEMO Project
Haemophilia
Enrolling by invitationObservational study
Patient Preferences in Treatment of Haemophilia A With and Without Inhibitors: a Discrete Choice Experiment in Germany
Haemophilia A
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.
Merel Timmer, PhD contact
Lize van Vulpen, MD, PhD principal investigator
University Medical Center Utrecht - Van Creveldkliniek
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Haemophilia and Hemophilia A, run by Van Creveldkliniek at 1 site 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 6 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lize van Vulpen, MD, PhD (+31887558450, l.f.d.vanvulpen-2@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- The primary objective of this study is to evaluate the diagnostic accuracy of physical examination and ultrasound to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 May 2026; AzTrials last refreshed its copy on 26 Oct 2026.