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Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens (PERSONAL)

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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
Sponsor:
Collaborator:
Baxter BioScience
Information provided by (Responsible Party):
Dr. Niamh O'Connell, St. James's Hospital, Ireland

Study Description
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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.

Condition or disease Intervention/treatment Phase
Severe Haemophilia A Drug: ADVATE [Antihemophilic Factor (Recombinant)] Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Number of subclinical haemarthroses [ Time Frame: 18 months ]
    The number of subclinical haemarthroses identifed on serial MRI scans of elbow, knee and ankle joints


Secondary Outcome Measures :
  1. EQ5D QoL score [ Time Frame: 18 months ]
    Comparison of score on EQ5D Quality of life questionnaire on standard versus PK tailored dosing

  2. 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

  3. IPAQ score [ Time Frame: 18 months ]
    Comparison of IPAQ activity scores (numeric) on standard versus PK tailored dosing

  4. Haemophilia joint health score (HJHS) [ Time Frame: 18 months ]
    Comparison of HJHS numeric score on standard versus PK tailored dosing

  5. Amount of FVIII usage (units) [ Time Frame: 18 months ]
    Comparison of FVIII usage in units on standard versus PK tailored dosing

  6. MRI joint score [ Time Frame: 18 months ]
    Comparison of joint score (numeric) determined on MRI by the International prophylaxis study group (IPSG) score

  7. Petterson joint score [ Time Frame: 18 months ]
    Comparison of Petterson joint score (numeric) on plain films for patients on standard versus PK tailored dosing

  8. Number of clinical haemarthroses [ Time Frame: 18 months ]
    Number of patient reported haemarthroses on standard prophylaxis versus PK tailored prophylaxis


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02314325


Contacts
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Contact: Michelle M Lavin, FRCPath +35314162142 mlavin@stjames.ie
Contact: Niamh M O'Connell, FRCPath +35314162142

Locations
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Ireland
St. James's Hospital Recruiting
Dublin, Ireland, D8
Principal Investigator: Niamh M O'Connell, FRCPath,PhD         
Sponsors and Collaborators
St. James's Hospital, Ireland
Baxter BioScience
Investigators
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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
More Information
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Responsible Party: Dr. Niamh O'Connell, Consultant Haematologist, St. James's Hospital, Ireland
ClinicalTrials.gov Identifier: NCT02314325    
Other Study ID Numbers: 2013-003240-23
First Posted: December 11, 2014    Key Record Dates
Last Update Posted: December 11, 2014
Last Verified: December 2014
Keywords provided by Dr. Niamh O'Connell, St. James's Hospital, Ireland:
Factor VIII deficiency
Arthropathy
MRI
 XRay
Joint
HJHS
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
 Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants