Objective part I: To detect subclinical (inflammatory) joint changes using ultrasound and MRI in severe haemophilia patients with low bleeding rates and to correlate these findings with biochemical markers of joint tissue turnover.Objective part II…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part I:
At joint level: Radiological signs of subclinical inflammation defined as
synovial hypertrophy on ultrasound (or MRI in case of inconclusive ultrasound
findings).
At patient level: Biomarkers for inflammation and biomarkers for cartilage and
bone turnover in blood and urine. The biomarkers comprising origin of different
joint tissues will be selected and adopted based on the literature on
osteoarthritis, which is a rapidly changing area of research.
Part II:
Radiological signs of subclinical bleeding defined as: synovial hypertrophy,
MRI detected iron / haemosiderin deposits in joints without a history of
bleeding at joint level.
Secondary outcome
At joint level:
- The diagnostic value of physical examination (swelling, warmth) in comparison
with synovial hypertrophy detected with ultrasound.
- Occurrence of MRI detectable blood products in joints with joint effusion on
ultrasound in the absence of a clinical bleed.
Background summary
Repeated provoked or spontaneous bleeding into the joints are the hallmark of
haemophilia. Recurrent or prolonged joint bleeds eventually lead to synovial
hypertrophy, progressive cartilage degradation and bone damage through
mechanical and inflammatory joint destruction. Treatment for severe haemophilia
is targeted at preventing joint bleeding using intravenous replacement therapy
with FVIII/IX (prophylaxis). In clinical practice, prophylaxis is constantly
adjusted, based on reported (joint) bleeding, joint assessment and measured
FVIII/IX (trough) levels.
There is some evidence, primarily based on X-ray and Magnetic Resonance Imaging
(MRI) studies, suggesting that patients with severe haemophilia may suffer from
subclinical bleeding. At the Van Creveldkliniek, patients who stopped
prophylaxis showed significant progression of arthropathy (joint scores and
X-ray) only after 10 years, despite very low reported bleeding rates.
Subclinical bleeding is expected to induce subclinical joint changes such as
synovial hypertrophy and inflammation, eventually resulting in osteochondral
changes and (progression of) arthropathy. Early detection of
subclinical/synovial and/or inflammatory joint changes will allow timely
adaptation/intensification of treatment to prevent irreversible damage.
Study objective
Objective part I:
To detect subclinical (inflammatory) joint changes using ultrasound and MRI in
severe haemophilia patients with low bleeding rates and to correlate these
findings with biochemical markers of joint tissue turnover.
Objective part II:
To evaluate whether there is any evidence of subclinical bleeding on MRI in
joints without a history of bleeding.
Study design
Cross-sectional study in a cohort of haemophilia patients aged >=16 years with
available longitudinal follow-up (patient records) at the Van Creveldkliniek,
UMC Utrecht.
Study burden and risks
Participating patients will spent more time in the hospital at the day of their
planned clinical follow-up due to the additional MRI examination. In addition
to possible clinically indicated blood test, additional blood samples (29ml)
will be drawn for biomarker evaluation and urine (30ml) will be collected.
Patients will not have a direct benefit from participating in this study: their
bleeding pattern and current outcome will not change. On long term, patients
may benefit from the optimization of treatment due to detailed assessment of
outcome and possibilities of treatment with anti-inflammatory drugs.
Heidelberglaan 100 100
Utrecht 3584 CX
NL
Heidelberglaan 100 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Patient provides written, informed consent;
- Born
o Between January 1, 1970 and January 1, 1988 (METC 11-442)
o After January 1, 1988 and age >=16 years
- Severe haemophilia A (FVIII< 0.01 IU/ml)
- Treated at the Van Creveldkliniek, UMC Utrecht
Exclusion criteria
- History of inhibitor development (>= 5 Bethesda Units* (BU) at any time or 1-
5 BU for >=1 year)
- Patients with a history of a major joint bleed in the three months prior to
assessment
- Patients with a history of a minor joint bleed in the month prior to
assessment
- MRI exclusion criteria, including MRI contraindications as per usual clinical
care, such as claustrophobia and metal or electronic implants not compatible
with MRI.
*One Bethesda unit (BU) is defined as that amount of inhibitor that results in
50% re-sidual FVIII:C activity in tested plasma mixed with an equal volume of a
normal plasma pool (NPP) after incubation for 2 hours at 37°C.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL68186.041.19 |