Haemophilia, Hemophilia A, Hemophilia B
Conditions
Keywords
Subclinical synovial proliferation, Ultrasound, MRI, Elastography
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
Interventions
OTHERUltrasound imaging
Ultrasound, MRI and elastography to screen for and follow subclinical synovial changes in ankle, elbow and knee.
Sponsors
Van Creveldkliniek
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| - 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| - 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)). | 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. |
| - 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. | 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 |
| - To evaluate the diagnostic accuracy of synovial elastography to identify active synovial proliferation in hemophilia patients with subclinical synovial hypertrophy | 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: |
Countries
Netherlands
Contacts
CONTACTLize van Vulpen, MD, PhD
CONTACTMerel Timmer, PhD
PRINCIPAL_INVESTIGATORLize van Vulpen, MD, PhD
University Medical Center Utrecht - Van Creveldkliniek
Outcome results
None listed