Severe Hemophilia A
Conditions
Keywords
hemophilia, prophylaxis, cost effectiveness
Brief summary
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
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).
Interventions
BIOLOGICALRecombinant Factor VIII (Advate/Helixate FS/KoegenateFS)
escalating dose prophylaxis
Sponsors
The Hospital for Sick Children
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Months to 30 Months
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Developed Target Joint Bleeding | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Factor Use | 12 months | annual factor usage per subject |
| Number of Patients Who Developed an Inhibitor to FVIII | 6 months | The number of patients who developed an inhibitor for FVIII, defined as \>= 0.5 Bethesda Units |
| Annualized Bleeding Rate | 6 months | Number of index hemarthorses (bleeds into ankles, elbows or knees) per patient per year |
| Joint Damage as Determined by the Physiotherapy Score | through study completion, a median of 10 years | 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 |
| Complications Arising From Indwelling Venous Catheter | 6 months | collect information on any complications relating to indwelling venous catheters that some subject use. |
| Physical Disability as Measured by the CHAQ | through study completion, a median of 10 years | 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. |
Countries
Canada
Participant flow
Recruitment details
Between June 26, 1997, and Jan 30, 2007, 56 boys were enrolled from 12 Canadian centres.
Participants by arm
| Arm | Count |
|---|---|
| Factor VIII escalating dose Factor VIII
Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS): escalating dose prophylaxis
Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS): escalating dose | 56 |
| Total | 56 |
Baseline characteristics
| Characteristic | Factor VIII |
|---|---|
| Age, Continuous | 1.6 years |
| Race/Ethnicity, Customized Race or Ethnic Group African Heritage | 1 Participants |
| Race/Ethnicity, Customized Race or Ethnic Group Asian | 2 Participants |
| Race/Ethnicity, Customized Race or Ethnic Group Middle Eastern | 1 Participants |
| Race/Ethnicity, Customized Race or Ethnic Group Mixed Aboriginal-Canadian | 5 Participants |
| Race/Ethnicity, Customized Race or Ethnic Group Mixed Latin-American | 3 Participants |
| Race/Ethnicity, Customized Race or Ethnic Group White European | 44 Participants |
| Region of Enrollment Canada | 56 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 56 |
| other Total, other adverse events | 0 / 56 |
| serious Total, serious adverse events | 0 / 56 |
Outcome results
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Factor VIII | Number of Participants Who Developed Target Joint Bleeding | 17 Participants |
Secondary
Annualized Bleeding Rate
Number of index hemarthorses (bleeds into ankles, elbows or knees) per patient per year
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Factor VIII | Annualized Bleeding Rate | 0.95 episodes per participant per year |
Secondary
Annualized Factor Use
annual factor usage per subject
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Factor VIII | Annualized Factor Use | 3600 IU/kg/year |
Secondary
Complications Arising From Indwelling Venous Catheter
collect information on any complications relating to indwelling venous catheters that some subject use.
Time frame: 6 months
Population: 25 participants had a central venous access device (CVAD) during the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Factor VIII | Complications Arising From Indwelling Venous Catheter | 0 Participants |
Secondary
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
Time frame: through study completion, a median of 10 years
Population: Median CCPES Score at study-end
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Factor VIII | Joint Damage as Determined by the Physiotherapy Score | Left Ankle | 1 units on a scale |
| Factor VIII | Joint Damage as Determined by the Physiotherapy Score | Right Ankle | 1 units on a scale |
| Factor VIII | Joint Damage as Determined by the Physiotherapy Score | Left Elbow | 0 units on a scale |
| Factor VIII | Joint Damage as Determined by the Physiotherapy Score | Right Elbow | 0 units on a scale |
| Factor VIII | Joint Damage as Determined by the Physiotherapy Score | Left Knee | 0 units on a scale |
| Factor VIII | Joint Damage as Determined by the Physiotherapy Score | Right Knee | 0 units on a scale |
Secondary
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
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Factor VIII | Number of Patients Who Developed an Inhibitor to FVIII | 5 Participants |
Secondary
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.
Time frame: through study completion, a median of 10 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Factor VIII | Physical Disability as Measured by the CHAQ | 0 units on a scale |