Canadian Hemophilia Prophylaxis Study

Study Overview
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Brief Summary
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Primary prophylaxis given less frequently initially, with the infusion frequency increased if needed (Escalating Dose Prophylaxis), is likely to be less expensive and associated with fewer complications than standard prophylaxis while reducing disability to a greater degree than intermittent therapy.

Detailed Description
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There are 2 specific study objectives. The first is to estimate the incidence of target joint bleeding in patients with severe hemophilia A treated (for primary prophylaxis) with Escalating Dose Prophylactic factor replacement. The second objective is to obtain accurate estimates of the direct and indirect costs associated with this protocol for use in a cost-effectiveness model (comparing Escalating Dose with standard prophylaxis and with intermittent therapy).

Official Title
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Moderate Term Musculoskeletal Outcomes With Escalating Dose Prophylaxis: the Canadian Hemophilia Prophylaxis Study Follow-up Study

Conditions
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Severe Hemophilia A

Intervention / Treatment
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* Biological: Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS)
* Biological: Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe hemophilia A (factor level less than 2%). Age greater than 1 year and less than or equal to 2.5 years. Normal joints using the World Federation of Hemophilia orthopedic scale. Normal radiographs of joints in which bleeding has occurred using the World Federation of Hemophilia radiographic scale. Platelet count of > 150,000. Informed consent to participate. Exclusion Criteria: Three or more clinically determined bleeds into any single elbow, knee or ankle. Presence or past history of a circulating inhibitor (level ≥ 0.5 Bethesda Units). Family judged to be non-compliant by the local hemophilia clinic director. Competing risk (symptomatic HIV infection, juvenile rheumatoid arthritis, metabolic bone disease, or other diseases known to cause or mimic arthritis.)

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 30 Months

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Factor VIII<br>escalating dose Factor VIII | Biological: Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS)<br>* escalating dose prophylaxis<br>* Other names: Recombinant Factor VIII (antihemophilic agent);Biological: Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS)<br>* escalating dose<br>* Other names: recombinant factor VIII (antihemophilic agent);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Developed Target Joint Bleeding | The number of participants who developed target joint bleeding during the study, which was defined as 3 bleeds into any 1 joint within a period of 3 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Bleeding Rate | Number of index hemarthorses (bleeds into ankles, elbows or knees) per patient per year | 6 months | 
| Annualized Factor Use | annual factor usage per subject | 12 months | 
| Number of Patients Who Developed an Inhibitor to FVIII | The number of patients who developed an inhibitor for FVIII, defined as >= 0.5 Bethesda Units | 6 months | 
| Physical Disability as Measured by the CHAQ | complete the Child Health Assessment Questionnaire (CHAQ) at each 6 month visit. The CHAQ is a validated tool to measure a disability index, with a possible score range of 0-3, where 0 represents no disability and 3 represents maximal disability. The CHAQ is known to have a strong ceiling effect. The CHAQ was collected at each study visit (i.e. every 6 months for the duration each patient was on study). The reported score represents the median end of study score. | through study completion, a median of 10 years | 
| Joint Damage as Determined by the Physiotherapy Score | Complete the modified Colarado Physiotherapy Assessment every 6 months at each visit with a score range 0-30 for ankles and knees and 0-26 for elbows), measured at all study visits, which we modified by not assessing crepitus or the ankle joint circumference measurement. For each scale, 0 represents no joint damage, with 26/30 representing maximum possible joint damage. The reported score represents the median end of study score | through study completion, a median of 10 years | 
| Complications Arising From Indwelling Venous Catheter | collect information on any complications relating to indwelling venous catheters that some subject use. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemophilia, prophylaxis, cost effectiveness