Comparison of Ideal vs. Actual Weight Base Factor Dosing

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.

Study Overview

• Status: Unknown
• Conditions: Hemophilia A
• Intervention / Treatment: Other: Ideal Body Weight First; Other: Actual Body Weight First

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heidi Thielmann, PhD; Phone Number: 206-689-6234; Email: hthielmann@bloodworksnw.org
• Study Contact Backup: Name: Rebecca Kruse-Jarres, MD, MPH; Phone Number: 206-689-6593; Email: RebeccaKr@BloodWorksNW.org

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Recruiting
      • Oregon Health & Science University
      • Contact: Michael Recht, MD, PhD; Phone Number: 503-494-8311; Email: rechtm@ohsu.edu
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital
      • Contact: Amanda Blair, MD; Phone Number: 206-987-2106; Email: Amanda.Blair@seattlechildrens.org
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Washington Center for Bleeding Disorders at Bloodworks Northwest
      • Contact: Rebecca Kruse-Jarres, MD, MPH; Phone Number: 206-689-6593; Email: RebeccaKr@BloodWorksNW.org
    • Spokane, Washington, United States, 99220-2555
      • Recruiting
      • Providence Sacred Heart Children's Hospital
      • Contact: Judy Felgenhauer, MD; Phone Number: 509-474-2777; Email: Judy.Felgenhauer@providence.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ideal Body Weight First; Randomized to receive factor product based on ideal body weight first	Other: Ideal 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)].
Experimental: Actual Body Weight First; Randomized to receive factor product based on actual body weight first	Other: Actual Body Weight First; Randomized to receive 50 U/kg (+/- 20%) of the factor product participants routinely use based on actual body weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery	Compare the recovery with FVIII between doses calculated on actual body weight versus ideal body weight in subjects with Hemophilia A	Change from baseline at up to two months
Underdosing	Determine the likelihood of underdosing when using ideal body weight	Change from baseline at up to two months
Overdosing	Determine the likelihood of overdosing when using actual body weight	Change from baseline at up to two months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of half-life	Determine the effect on half-life of these dosing strategies	Change from baseline at up to two months
Effect on hemophilia severity	Determine the effect of pharmacokinetic differences 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
Regular half-life vs. extended half-life Regular half-life vs. extended half-life	Determine differences in participants receiving regular half-life versus extended half-life products	Change from baseline at up to two months
Overweight vs. obese	Determine the differences, if any, between overweight and obese participants	Change from baseline at up to two months

Collaborators and Investigators

• Sponsor: Bloodworks
• Collaborators: Oregon Health and Science University; Seattle Children's Hospital; Providence Health & Services

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: August 9, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): September 18, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: FVIII; Hemophilia A; Ideal body weight; Actual body weight
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: BDC Ideal Body Weight Dosing

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No