Phase 4
N=63
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
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT00357656 ↗Enrolled (actual)
63
Serious AEs
13.9%
Results posted
May 2017
Primary outcome: Primary: 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) — 3.632; 3.383; 3.718; 2.855 Tera per Liter — p=0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Recombinant Protein-Free Factor VIII (rAHF-PFM) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Oct 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
3.632; 3.383; 3.718; 2.855; 3.548; 3.345 | 0.001 sig |
| SECONDARY Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon |
709.28; 811.11; 724.48; 265; 814.03; 819.22 | — |
| SECONDARY Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon |
766.73; 929.49; 752.91; 341.5; 1000.37; 899.83 | — |
| SECONDARY Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion |
0.10; 0.03; 0.08; 0.50; 0.00; 0.00 | — |
| SECONDARY Number of Units of Packed Red Blood Cells Transfused |
0.9; 1.3; 1.0; 1.5; 0.2; 1.2 | — |
| SECONDARY Number of Adverse Events Related to the Administration of the Study Product. |
6; 8; 14 | — |
| SECONDARY Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation) |
2; 2; 4 | — |
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.
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 = 200 cells/mm³ (CD4 count at screening), but HIV negative subjects with a CD4 count = 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.
Data sourced from ClinicalTrials.gov (NCT00357656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.