Severe Haemophilia A Clinical Trial
Official title:
Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens
This trial is designed to assess if there is evidence of subclinical joint bleeding on MRI/X-Ray in adults with severe Haemophilia A while on standard and/or pharmacokinetically tailored prophylaxis regimens. Participants with severe Haemophilia A will have longitudinal MRI and XRay imaging of their elbows, ankles and knees at 0, 6 and 18 months while on standard ( 0-6 months) and then pharmacokinetically tailored (7-18 months) recombinant Factor VIII prophylaxis.
Subclinical joint bleeding (SJB) in Haemophilia may cause early and progressive joint
damage. Clinical haemarthrosis is a traditional outcome measure in Haemophilia trials but
may not always correlate with the degree of arthropathy. Even in the absence of
haemarthrosis, abnormalities may be detected on MRI. MRI offers greater sensitivity than
physical examination for early joint damage and use of the International Prophylaxis Study
Group (IPSG) score allows standardisation across clinical trials. Early awareness of
haemophiliac arthropathy can prompt intervention with physiotherapy, specific exercise
programmes, optimization of prophylaxis and orthotics to improve overall joint outcomes.
The time spent with Factor VIII (FVIII) levels <0.01 IU/mL is a known risk for bleeding.
Conventional prophylaxis schedules follow a weight based regimen and are titrated according
to clinical bleeds. FVIII pharmacokinetics (PK) may be used to optimise FVIII prophylactic
regimens, maintaining adequate FVIII trough levels. This offers the possibility to not only
tailor individual regimens but also may potentially reduce the rate of clinical and
subclinical joint bleeding.
This is a national, investigator led clinical trial investigating the feasibility of PK
tailored prophylaxis in adults with severe Haemophilia A. This trial will prospectively and
longitudinally assess SJB and joint health in Irish adults with severe Haemophilia A.
SJB will be compared while on standard (weight based, 20-40 IU/kg) and PK tailored
prophylaxis(maintaining trough FVIII > 0.015 IU/mL). This is a crossover study will
participants spending months 0-6 on standard prophylaxis and then changing over to PK
tailored dosing for months 7-18. A comprehensive joint assessment involving bleed history,
clinical examination, physical activity, specialist physiotherapy review, X-rays and MRI
scanning of bilateral ankles, knees and elbow will be performed at months 0,6 and 18.
Haemophilia Joint Health Score (HJHS), International Physical Activity (IPAQ) and EuroQoL
5-Dimensions (EQ5D) Questionnaires will also be performed at these three timepoints.
Clinical bleeds and FVIII usage will be recorded throughout the trial using the
investigators Home Scan system, a smart phone application that allows patients to log factor
VIII usage.
Results will be compared between both arms and between participants on primary and secondary
prophylaxis. Information on those with naïve joints versus established arthropathy will be
compared.
Due to the relative rarity of severe Haemophilia A the investigators plan to recruit 20
patients in total. All patients will act as their own control, crossing over from standard
to PK tailored prophylaxis with joint assessments prior to crossover to allow comparison of
the two regimes.
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Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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