Clinical trial NCT06809972: Synovial Proliferation on Routine Ultrasound: Active or Inactive?
Official title: Synovial Proliferation on Routine Ultrasound: Active or Inactive? A Prospective Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Haemophilia
Hemophilia A
Hemophilia B
Keywords: Subclinical synovial proliferation
Ultrasound
MRI
Elastography
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2025-02-05
Enrollment: 46
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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

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.

Primary outcomes:
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.
timeFrame: 12 weeks
Secondary outcomes:
measure: - 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)).
timeFrame: 12 weeks
measure: - 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.
timeFrame: 12 weeks
measure: - To evaluate the diagnostic accuracy of synovial elastography to identify active synovial proliferation in hemophilia patients with subclinical synovial hypertrophy
timeFrame: 12 weeks
Other outcomes:
measure: - To describe elastographic differences between active clinical synovitis, active subclinical synovial hypertrophy and inactive subclinical hypertrophy.
timeFrame: At baseline (week 0) without follow-up
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: University Medical Center Utrecht - Van Creveldkliniek
name: Lize van Vulpen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: