Hemophilia A
Conditions
Keywords
Hemophilia A, FVIII, Ideal body weight, Actual body weight
Brief summary
This is a randomized, prospective, multicenter study to examine whether or not the current recommended factor dosing strategy - i.e., dosing by actual body weight - in overweight and obese patients with Hemophilia A may deliver excessive clotting factor to achieve the desired result of bleeding prevention and cessation. This study also examines ways to prevent delivering excessive factor by using a patient's ideal body weight as a new dosing strategy compared to the current dosing strategy. The hypothesis being tested is that factor dosing based on ideal body weight will result in protective factor levels.
Detailed description
This is a randomized, prospective, multicenter, open-label, crossover study to examine whether or not the current recommended factor dosing strategy, i.e., dosing by actual body weight in overweight and obese patients, may deliver more clotting factor than necessary to cause bleeding to stop in participants with Hemophilia A who use Factor VIII (FVIII). This study also examines ways to prevent delivering too much factor by using a participant's ideal body weight as a new dosing strategy compared to the current dosing strategy. The hypothesis being tested is that factor dosing based on ideal body weight will result in hemostatic factor levels. The study will be conducted at the Washington Center for Bleeding Disorders (WCBD) at Bloodworks Northwest, Oregon Health & Science University (OHSU), Seattle Children's Hospital (SCH), and Providence Sacred Heart Children's Hospital (SH). Cumulatively across the four sites, up to 20 participants will be enrolled. Randomization will be performed centrally at WCBD. Participants will provide their own factor. Prior to the first study-related dose, participants will stop taking any FVIII products for either 48 hours if currently using a short-acting FVIII product or 72 hours for a long acting FVIII product. Factor levels will be measured immediately before and at multiple points after two different factor doses. Subjects will be randomized to start their dosage based either on actual body weight or ideal body weight first and then crossover to receive dosage based on the other category.
Interventions
OTHERIdeal Body Weight First
Randomized to receive 50 U/kg (+/- 20%) of the factor product participants routinely use based on ideal body weight. For participants age 12-19, ideal weight is calculated using the McLaren method. For participants age 20 and over, ideal weight is calculated using the following equation: \[50kg + (2.3kg\*every inch over 5 feet)\].
OTHERActual Body Weight First
Randomized to receive 50 U/kg (+/- 20%) of the factor product participants routinely use based on actual body weight.
Sponsors
Seattle Children's Hospital
Oregon Health and Science University
Providence Health & Services
Bloodworks
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Subjects are randomized to receive factor based either on ideal body weight or actual body weight first followed by receiving factor based on the other category next
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hemophilia A * Able and willing to comply with pharmacokinetic testing schedule * Either overweight or obese BMI using CDC definitions by age
Exclusion criteria
* Inhibitor of \> 0.6 BU twice in the past, or documented abnormal recovery of less than 66% (of expected) in the past * Known other bleeding disorder * Known other prolongation in aPTT (lupus anticoagulant, FXII deficiency) * Female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery | Change from baseline at up to two months | Compare the recovery with FVIII between doses calculated on actual body weight versus ideal body weight in subjects with Hemophilia A |
| Underdosing | Change from baseline at up to two months | Determine the likelihood of underdosing when using ideal body weight |
| Overdosing | Change from baseline at up to two months | Determine the likelihood of overdosing when using actual body weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of half-life | Change from baseline at up to two months | Determine the effect on half-life of these dosing strategies |
| Overweight vs. obese | Change from baseline at up to two months | Determine the differences, if any, between overweight and obese participants |
| Effect on hemophilia severity | Change from baseline at 20-40 minutes, 5-7 hours, 20-26 hours, and 44-50 hours for both half-life and extended half-life and also at 69-75 hours, and 93-99 hours for extended half-life | Determine the effect of pharmacokinetic differences on hemophilia severity |
| Regular half-life vs. extended half-life Regular half-life vs. extended half-life | Change from baseline at up to two months | Determine differences in participants receiving regular half-life versus extended half-life products |
Countries
United States
Contacts
Primary ContactHeidi Thielmann, PhD
Backup ContactRebecca Kruse-Jarres, MD, MPH
Outcome results
None listed