Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:
Sponsor: Baxalta US Inc.

Current 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) [ Time Frame: During the first postoperative 24 hours every 8 hours ± 30 minutes the drainage fluid was to be recorded.. ]

Original Primary Outcome:

Current Secondary Outcome:

• Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon [ Time Frame: During the first 24 postoperative hours blood loss was measured every 8 hours ± 30 minutes ]

  Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject 1) for the intraoperative procedure (defined as the time period from incision to application of compressive dressing and release of tourniquet, if applicable), 2) for the first 24 hours postoperatively, and 3) for the postoperative period until drain removal, if drainage continued beyond 24 hours.

  Units: Milliliter of blood

• Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon [ Time Frame: From end of surgery (application of compressive dressing and release of tourniquet, if applicable) until drain removal (up to postoperative day 7). ]

  The total blood loss for the postoperative period (from end of surgery until drain removal) was adjusted for the expected blood loss by applying a log-transformation of the blood loss data.

  The drainage volume was measured every 8 hours +/- 30 minutes during the first 24 hours. If the drainage continued beyond 24 hours, the PRBC volume and hemoglobin was to be measured cumulatively every 24 hours or whenever the drainage bottle was emptied and at the time of drain removal. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject for the first 24 hours postoperatively, and for the postoperative period until drain removal, if drainage continued beyond 24 hours.

  Units: Milliliter of blood

• Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion [ Time Frame: Through Postoperative Day 7 ]
  To simplify the results below: Bleeding episodes were reported for 4 subjects (3 subjects on bolus infusion: 2 in Stratum A and 1 in Stratum B, and 1 subject on continuous infusion/Stratum B). The 4 subjects had 1 bleeding episode each. No bleeding episodes were reported for Stratum C.
• Number of Units of Packed Red Blood Cells Transfused [ Time Frame: During the first postoperative 24 hours ]
• Number of Adverse Events Related to the Administration of the Study Product. [ Time Frame: From first study drug exposure until study completion/discontinuation (approximately 9-26 weeks per subject) ]
  All AEs from the first study drug exposure until the study completion/discontinuation date were to be recorded. Each AE was to be evaluated by the investigator for causal relationship (i.e., unrelated, possibly related or probably related) to the study product.
• Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation) [ Time Frame: Throughout the study period of approximately 9-26 weeks per participant ]
  Number of participants that developed Factor VIII inhibitory antibody during the study.

Original Secondary Outcome:

Information By: Baxalta US Inc.

Dates:
Date Received: July 25, 2006
Date Started: June 1, 2006
Date Completion:
Last Updated: April 12, 2017
Last Verified: January 2017