Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens (PERSONAL)
|ClinicalTrials.gov Identifier: NCT02314325|
Recruitment Status : Unknown
Verified December 2014 by Dr. Niamh O'Connell, St. James's Hospital, Ireland.
Recruitment status was: Recruiting
First Posted : December 11, 2014
Last Update Posted : December 11, 2014
|Condition or disease||Intervention/treatment||Phase|
|Severe Haemophilia A||Drug: ADVATE [Antihemophilic Factor (Recombinant)]||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens|
|Study Start Date :||April 2014|
|Estimated Primary Completion Date :||May 2016|
|Estimated Study Completion Date :||October 2016|
Active Comparator: Standard prophylaxis
Advate [Antihemophilic Factor(Recombinant)] 20-40 IU/kg 5-7 infusions per 14days
Drug: ADVATE [Antihemophilic Factor (Recombinant)]
In Arm 1 prior patients will be dosed as per body weight 20-40 IU/kg 5-7 infusions per fortnight
Experimental: Pharmacokinetic tailored prophylaxis
Advate [Antihemophilic Factor(Recombinant)] dose determined by individual patient pharmacokinetics and infusions administerd on alternate days
Drug: ADVATE [Antihemophilic Factor (Recombinant)]
In Arm 2 patients who have completed arm 1 will cross over onto an individualised PK tailored alternate day dosing regimen
- Number of subclinical haemarthroses [ Time Frame: 18 months ]The number of subclinical haemarthroses identifed on serial MRI scans of elbow, knee and ankle joints
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02314325
|Contact: Michelle M Lavin, FRCPathfirstname.lastname@example.org|
|Contact: Niamh M O'Connell, FRCPath||+35314162142|
|St. James's Hospital||Recruiting|
|Dublin, Ireland, D8|
|Principal Investigator: Niamh M O'Connell, FRCPath,PhD|
|Principal Investigator:||Niamh M O'Connell, PhD, FRCPath||St. James's Hospital, Dublin|
|Principal Investigator:||James O'Donnell, PhD, FRCPath||St. James's Hospital, Dublin|