Clinical Trial: Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens

Study Status: Active, not recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens

Brief Summary: 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.

Detailed Summary:

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 examin
Sponsor: St. James's Hospital, Ireland

Current Primary Outcome: Number of subclinical haemarthroses [ Time Frame: 18 months ]

The number of subclinical haemarthroses identifed on serial MRI scans of elbow, knee and ankle joints


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • EQ5D QoL score [ Time Frame: 18 months ]
    Comparison of score on EQ5D Quality of life questionnaire on standard versus PK tailored dosing
  • Percentage of prescribed doses of prophylaxis taken [ Time Frame: 18 months ]
    The number of missed doses of prophylaxis on the standard and PK tailored dosing regimens
  • IPAQ score [ Time Frame: 18 months ]
    Comparison of IPAQ activity scores (numeric) on standard versus PK tailored dosing
  • Haemophilia joint health score (HJHS) [ Time Frame: 18 months ]
    Comparison of HJHS numeric score on standard versus PK tailored dosing
  • Amount of FVIII usage (units) [ Time Frame: 18 months ]
    Comparison of FVIII usage in units on standard versus PK tailored dosing
  • MRI joint score [ Time Frame: 18 months ]
    Comparison of joint score (numeric) determined on MRI by the International prophylaxis study group (IPSG) score
  • Petterson joint score [ Time Frame: 18 months ]
    Comparison of Petterson joint score (numeric) on plain films for patients on standard versus PK tailored dosing
  • Number of clinical haemarthroses [ Time Frame: 18 months ]
    Number of patient reported haemarthroses on standard prophylaxis versus PK tailored prophylaxis


Original Secondary Outcome: Same as current

Information By: St. James's Hospital, Ireland

Dates:
Date Received: September 3, 2014
Date Started: April 2014
Date Completion: October 2016
Last Updated: December 10, 2014
Last Verified: December 2014