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NCT Number: NCT06809972

Synovial Proliferation on Routine Ultrasound: Active or Inactive?

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).

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Key information

Conditions

Haemophilia Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Hematologic Diseases Hemic and Lymphatic Diseases Hemophilia A Hemophilia B Hemorrhagic Disorders

Age range

12 year and older

Sex eligibility

Male

Study type

Observational

Primary location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location status: Recruiting

Location contact

Lize van, MD, PhD

CONTACT

[email protected]

+31887558450

Merel Timmer, PhD

SUB_INVESTIGATOR

Wouter Foppen, MD, PhD

SUB_INVESTIGATOR

About this study

To be completed

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ultrasound imaging

Other

Ultrasound, MRI and elastography to screen for and follow subclinical synovial changes in ankle, elbow and knee.

Other names: MRI, Elastography

Primary outcomes

  1. - 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

Secondary outcomes

  1. - 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

    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.

  2. - 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

    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

  3. - To evaluate the diagnostic accuracy of synovial elastography to identify active synovial proliferation in hemophilia patients with subclinical synovial hypertrophy

    Time frame: 12 weeks

    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:

Other outcomes

  1. - To describe elastographic differences between active clinical synovitis, active subclinical synovial hypertrophy and inactive subclinical hypertrophy.

    Time frame: At baseline (week 0) without follow-up

    For the side objective a group of patients with active clinical synovitis will only undergo elastography and be used as positive control in elastography-analysis, no other measurement nor analysis will be performed.

Study contacts

Contact information is provided by the study sponsor or research team.

Lize van Vulpen, MD, PhD

CONTACT

[email protected]

+31887558450

Merel Timmer, PhD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Van Creveldkliniek

Other

Registry information

Official study title

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

Acronym: 2BEGIN

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Feb 5, 2025
Registry last updated
May 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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