Brief Title
Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens
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 Description
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.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Number of subclinical haemarthroses
Secondary Outcome
EQ5D QoL score
Condition
Severe Haemophilia A
Intervention
ADVATE [Antihemophilic Factor (Recombinant)]
Study Arms / Comparison Groups
Standard prophylaxis
Description: Advate [Antihemophilic Factor(Recombinant)] 20-40 IU/kg 5-7 infusions per 14days
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
April 2014
Completion Date
October 2016
Primary Completion Date
May 2016
Eligibility Criteria
Inclusion Criteria:
- Male patients with severe Haemophilia A (baseline Factor VIII level of <0.01 IU/mL)
- Age 18 years and above
- Patients taking any regular prophylactic regimen (defined as regular factor VIII
infusions, at least 5 times a fortnight, with the aim of minimising haemarthroses and
other clinically significant bleeds).
- Low titre inhibitors, past history of an inhibitor, abnormal liver function, drugs
that interfere with haemostasis and low Cluster of Differentiation 4 (CD4) counts are
allowed.
Exclusion Criteria:
- Presence of a target joint on prophylaxis (defined as 3 bleeds into one joint, during
a 6 month period, during the last year).
- The occurrence of more than 3 haemarthroses in the last year that required more than 2
infusions to resolve.
- Patients with a learning disability or dementia
- Prisoners
- Adults who are unconscious/unable to give informed consent
- Participants with a pacemaker or implanted medical devices which are unsuitable to
have a MRI will be excluded from the MRI scans during the trial but may proceed with
other components.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Niamh M O'Connell, PhD, FRCPath, +35314162142, [email protected]
Location Countries
Ireland
Location Countries
Ireland
Administrative Informations
NCT ID
NCT02314325
Organization ID
2013-003240-23
Responsible Party
Principal Investigator
Study Sponsor
St. James's Hospital, Ireland
Collaborators
Baxter BioScience
Study Sponsor
Niamh M O'Connell, PhD, FRCPath, Principal Investigator, St. James's Hospital, Dublin
Verification Date
December 2014