Brief Title
Phase 3/4 Study of a Recombinant Protein-Free Factor VIII (rAHF-PFM): Comparison of Continuous Infusion Versus Intermittent Bolus Infusion in Hemophilia A Subjects Undergoing Major Orthopedic Surgery
Official Title
Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method (rAHF PFM): A Phase 3/4, Prospective, Controlled, Randomized, Multi-Center Study to Compare the Efficacy and Safety of Continuous Infusion (CI) Versus Intermittent Bolus Infusion (BI) in Subjects With Severe or Moderately Severe Hemophilia A Undergoing Major Orthopedic Surgery
Brief Summary
The purpose of this study is to compare the hemostatic efficacy and safety of continuous
infusion versus intermittent bolus infusion in the peri- and post-operative setting,
employing rAHF-PFM, a recombinant antihemophilic factor manufactured without added human or
animal proteins, in previously treated patients with severe or moderately severe hemophilia A
(baseline factor VIII level <= 2% of normal) who are undergoing unilateral major orthopedic
surgery that requires drain placement. The total study period per subject (from consent to
study completion) will vary from approximately 9 to 26 weeks and will involve clinical and
laboratory assessments.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI)
Secondary Outcome
Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon
Condition
Hemophilia A
Intervention
Recombinant Protein-Free Factor VIII (rAHF-PFM)
Study Arms / Comparison Groups
BI
Description: Bolus infusion of rAHF-PFM
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
85
Start Date
May 29, 2006
Completion Date
December 9, 2015
Primary Completion Date
October 1, 2015
Eligibility Criteria
Inclusion Criteria:
- The subject or the subject's legally authorized representative has provided signed
informed consent.
- The subject is within 18 to 70 years of age.
- The subject has severe or moderately severe hemophilia A, defined by a baseline factor
VIII level <= 2% of normal, as tested at screening. A subset of 15 subjects per group
must have baseline factor VIII levels < 1% of normal.
- The aPTT must be within the range of normal after administration of FVIII concentrate,
as determined in the preoperative pharmacokinetic evaluation, or as documented in the
medical history, if available.
- The subject is scheduled to undergo an elective unilateral major orthopedic surgery
that requires drain placement.
- The subject was previously treated with factor VIII concentrate(s) for a minimum of at
least 150 exposure days (as estimated by the investigator) prior to study entry.
- Human immunodeficiency virus (HIV) positive subjects must be immunocompetent as
determined with a CD4 count >= 200 cells/mm³ (CD4 count at screening), but HIV
negative subjects with a CD4 count < 200 cells/mm³ qualify, if immunocompetency is
documented.
- The subject has a life expectancy of at least 28 days from the day of surgery.
Exclusion Criteria:
- The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4
BU (Nijmegen modification of the Bethesda assay) in the central laboratory.
- The subject has a history of factor VIII inhibitors with a titer >= 0.4 BU (by
Nijmegen assay) or >= 0.5 BU (by Bethesda assay) at any time prior to screening.
- The subject is scheduled to undergo any other concurrent minor or major surgery during
the course of the study. The placement of central venous lines and the performance of
fine needle aspiration biopsies are permitted.
- Excluding hemophilia-related physical impairments, the subject is assigned to NYHA
class >= III according to the New York Heart Association (NYHA).
- The subject has an abnormal renal function (serum creatinine > 1.5 mg/dL).
- The subject has active hepatic disease (alanine aminotransferase [ALT] or aspartate
aminotransferase [AST] levels > 5 times the upper limit of normal).
- The subject has severe chronic liver disease as evidenced by, but not limited to, any
of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal
vein hypertension including presence of otherwise unexplained splenomegaly and history
of esophageal varices.
- The subject has clinical and/or laboratory evidence of abnormal hemostasis from causes
other than hemophilia A (e.g., late-stage chronic liver disease, immune
thrombocytopenia purpura).
- The subject is currently receiving, or is scheduled to receive during the course of
the study, an immunomodulating drug other than anti-retroviral chemotherapy (e.g.,
alpha-interferon, corticosteroid agents at a dose equivalent to hydrocortisone greater
than 10 mg/day).
- The subject has a known hypersensitivity to mouse or hamster proteins.
- The subject has received another investigational drug study within 30 days prior to
screening and/or is scheduled to receive additional investigational drug during the
course of the trial in the context of another investigational study.
- The subject is identified by the investigator as being unable or unwilling to
cooperate with study procedures.
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Study Director, ,
Location Countries
Austria
Location Countries
Austria
Administrative Informations
NCT ID
NCT00357656
Organization ID
060402
Secondary IDs
2005-005697-71
Responsible Party
Sponsor
Study Sponsor
Baxalta now part of Shire
Collaborators
Baxalta Innovations GmbH, now part of Shire
Study Sponsor
Study Director, Study Director, Takeda
Verification Date
April 2021