Is synovial proliferation in haemophilia joints active or inactive?

Synovial Proliferation on Routine Ultrasound: Active or Inactive? A Prospective Study

This project will test whether ultrasound, MRI and elastography can tell if subclinical synovial proliferation in people with severe haemophilia is currently active so clinicians can treat earlier.

Quick facts

• Study type: Observational
• Enrollment: 46 (estimated)
• Ages: 12 Years and up
• Sex: Male
• Sponsor: UMC Utrecht (Academic / other)
• Locations: 1 site (Utrecht)
• Trial ID: NCT06809972 on ClinicalTrials.gov

What this trial studies

This observational study follows males aged 12 and older with severe haemophilia A or B who have subclinical synovial proliferation in at least one knee, ankle, or elbow identified on routine ultrasound. Participants receive physical examination and advanced imaging (ultrasound, MRI, and elastography) and are monitored for up to 12 weeks while continuing standard-of-care coagulation factor replacement and optional celecoxib. The study aims to classify synovial proliferation as active or inactive using clinical findings and imaging signatures. No experimental drug is given; the focus is on characterizing imaging markers that may indicate ongoing subclinical joint bleeding.

Who should consider this trial

Good fit: Male patients aged 12 or older with severe haemophilia A or B who have subclinical synovial proliferation in one or more knees, ankles, or elbows confirmed by routine ultrasound and who can give informed consent.

Not a fit: Patients with a recent bleed in the joint of interest, prosthetic or fused joints in that location, confirmed inflammatory arthritis, or other major exclusions (such as active inhibitors) are unlikely to benefit from the imaging classification in this protocol.

Why it matters

Potential benefit: If successful, this approach could help clinicians detect active subclinical joint disease earlier and start or adjust treatment to prevent long-term joint damage.

How similar studies have performed: Prior work has shown imaging can detect subclinical synovial changes in haemophilia, but combining MRI, ultrasound, and elastography for short-term monitoring of activity is relatively novel and not yet widely validated.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Utrecht

• University Medical Center Utrecht — Utrecht, Netherlands (Recruiting)

Study contacts

• Principal investigator: Lize van Vulpen, MD, PhD — University Medical Center Utrecht - Van Creveldkliniek
• Study coordinator: Lize van Vulpen, MD, PhD

Conditions Haemophilia; Hemophilia A; Hemophilia B; Subclinical synovial proliferation; Ultrasound; MRI; Elastography