Synovial Proliferation on Routine Ultrasound: Active or Inactive?
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexMale
Age12+
SponsorVan Creveldkliniek
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Gender: male
Patients with severe haemophilia A or B
Treated with registered prophylaxis medication including coagulation factors and by- passing agents.
Age ≥ 12 years
Disqualifiers
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.
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Ultrasound imaging
Other interventionUltrasound, MRI and elastography to screen for and follow subclinical synovial changes in ankle, elbow and knee.
Treatment groups
No treatment groups listed
Trial outcomes
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.
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
Time frame
12 weeksSecondary 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)).
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.
Time frame
12 weeks2
- 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
Time frame
12 weeks3
- 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:
Time frame
12 weeksOther outcomes
1
- To describe elastographic differences between active clinical synovitis, active subclinical synovial hypertrophy and inactive subclinical hypertrophy.
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.
Time frame
At baseline (week 0) without follow-upSponsors and contacts
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Van Creveldkliniek
Lead sponsor
UMC Utrecht
Sponsor institution
Source ClinicalTrials.gov