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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Baxter Healthcare Corporation
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00357656
First received: July 25, 2006
Last updated: March 6, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to compare the hemostatic efficacy and safety of continuous infusion versus intermittent bolus infusion in the intra- 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 replacement. The total study period per subject (from consent to study completion) will vary from approximately 9 to 18 weeks and will involve clinical and laboratory assessments.


Condition Intervention Phase
Hemophilia A
Drug: Recombinant Protein-Free Factor VIII (rAHF-PFM)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Comparison of the cumulative packed red blood cell (PRBC) volume in the drainage fluid during 24 hours following surgery in subjects receiving rAHF-PFM by bolus infusion or continuous infusion [ Time Frame: 24 hours following surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total amount of hemoglobin in the cumulative drainage fluid [ Time Frame: During the first postoperative 24 hours (and until time of drain removal, if drainage continues beyond 24 hours) ] [ Designated as safety issue: No ]
  • Actual postoperative blood loss [ Time Frame: During the first postoperative 24 hours ] [ Designated as safety issue: No ]
  • Number of bleeding episodes during treatment with continuous or bolus infusion [ Time Frame: Postoperative Day 7 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: June 2006
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI
Bolus infusion of rAHF-PFM
Drug: Recombinant Protein-Free Factor VIII (rAHF-PFM)
The treatment schedule for intermittent BI of rAHF-PFM will begin with the administration of the loading dose according to the dose recommendations provided by the sponsor. If required by the hemostatic challenge, additional boluses may be administered after a blood sample for FVIII determination has been drawn. All infusions of rAHF PFM will be given over a period <= 5 minutes (maximum infusion rate, 10 mL/min).
Experimental: CI
Continuous infusion of rAHF-PFM
Drug: Recombinant Protein-Free Factor VIII (rAHF-PFM)

An initial loading dose will be administered intravenously over a period <= 5 minutes (maximum of infusion rate of 10 mL/minute) within 60 minutes prior to surgery dose in order to maintain a minimum target FVIII level of at least 80% of normal.

CI will start prior to surgery as soon as the loading dose has been administered, at a rate calculated according to a formula provided by the sponsor.

All study product must be administered with a syringe pump running at an infusion rate according to the dosing regimen, but always >= 0.4 mL/h.


  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357656

Contacts
Contact: Richard Steinbrugger, Clinical Project Manager richard_steinbrugger@baxter.com

  Show 30 Study Locations
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Isabella Presch, MD Baxter Healthcare Corporation
  More Information

No publications provided

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00357656     History of Changes
Other Study ID Numbers: 060402
Study First Received: July 25, 2006
Last Updated: March 6, 2013
Health Authority: Austria: Federal Ministry for Health and Women
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Ministry of Health and Consumption
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Baxter Healthcare Corporation:
Hemophilia A (severe or moderately severe)

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014