Effect of Aprotinin on Transfusion Requirements and Blood Loss in Patients Undergoing Elective Primary Total Hip Replacement

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, 2-Arm Study to Investigate the Effect of Aprotinin on Transfusion Requirements and Blood Loss in Patients Undergoing Elective Primary Total Hip Replacement Surgery

The purpose of this study is to assess if aprotinin (BAY A0128), given intravenously during surgery, is safe and can help reduce the amount of bleeding and the need for a blood transfusion during hip replacement surgery. Patients undergoing major surgery are at risk for significant blood loss. Because of this, there is a need for drugs that will help slow the amount of bleeding during surgery.

Study Overview

• Status: Completed
• Conditions: Blood Loss, Surgical
• Intervention / Treatment: Drug: Trasylol (Aprotinin, BAYA0128); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1L 3L5
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1T2
    • Vancouver, British Columbia, Canada, V6Z 1Y6
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 5N5
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
  • Ontario
    • Guelph, Ontario, Canada, N1E 4J4
    • Kitchener, Ontario, Canada, N2G 1G3
    • London, Ontario, Canada, N6A 5A5
    • Oshawa, Ontario, Canada, L1G 2B9
    • Oshawa, Ontario, Canada, L1J 2J2
    • Richmond Hill, Ontario, Canada, L4C 4Z3
• Puerto Rico
  • San Juan, Puerto Rico, 00935
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Phoenix, Arizona, United States, 85023
  • California
    • La Jolla, California, United States, 92037
    • San Diego, California, United States, 92123
  • Colorado
    • Aurora, Colorado, United States, 80012
  • Connecticut
    • Farmington, Connecticut, United States, 06032
  • Florida
    • Bay Pines, Florida, United States, 33744
    • Jacksonville Beach, Florida, United States, 32250
    • Sarasota, Florida, United States, 34239
    • St. Petersburg, Florida, United States, 33703
  • Idaho
    • Boise, Idaho, United States, 83702
  • Indiana
    • Indianapolis, Indiana, United States, 46260
    • Mooresville, Indiana, United States, 46158
  • Iowa
    • Iowa City, Iowa, United States, 52242-1089
  • Maryland
    • Baltimore, Maryland, United States, 21215
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
    • Ypsilanti, Michigan, United States, 48197
  • North Carolina
    • Durham, North Carolina, United States, 27710
    • Greensboro, North Carolina, United States, 27401
  • Oregon
    • Bend, Oregon, United States, 97701
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
    • Pittsburgh, Pennsylvania, United States, 15213-2592
  • Texas
    • Dallas, Texas, United States, 75231
    • Lubbock, Texas, United States, 79410
    • San Antonio, Texas, United States, 78233

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects requiring elective primary total hip replacement surgery
• Documented, signed, dated informed consent obtained prior to any study specific procedures being performed

Exclusion Criteria:

• Subjects with previous exposure to aprotinin in the last 6 months. If the subject has undergone cardiac surgery in the last 6 months, all attempts should be made to ascertain if aprotinin was administered during cardiac surgery. If no records are available, subject should be excluded. If during cardiac surgery in the last 6 months, there is a record of aprotinin administration, subject should be excluded
• Subjects with a known or suspected allergy to aprotinin - Subjects with impaired renal function (serum creatinine > 3.5 mg/dl or 309 micromoles/liter)
• Subjects with a history of bleeding diathesis or known coagulation factor deficiency
• Subjects with failure of a major organ system or any active significant medical illness that in the opinion of the investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study
• Subjects who refuse to receive allogenic blood products for religious or other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Trasylol (Aprotinin, BAYA0128); A loading dose IV infusion of 2,000,000 KIU (200 mL) followed by 500,000 KIU (50 mL) IV per hour until the end of surgery of aprotinin using an IV infusion pump
Placebo Comparator: Arm 2	Drug: Placebo; A loading dose IV infusion of 2,000,000 KIU (200 mL) followed by 500,000 KIU (50 mL) IV per hour until the end of surgery of of placebo using an IV infusion pump

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent of subjects requiring a blood transfusion (predonated blood or packed red blood cells, autologous or allogenic) anytime in the intra-operative or post-operative period (up to the earlier of Day 7 or discharge)	intra-op tp discharge

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in blood markers related to inflammation and blood coagulation	surgery to discharge
The percent of subjects receiving an allogenic transfusion of blood or packed red cells during surgery and up to the earlier of Day 7 or discharge.	surgery to discharge
The percent of subjects who did and did not predonate blood receiving an allogenic transfusion of blood or packed red cells during surgery and up to the earlier of Day 7 or discharge.	surgery to discharge
The number of units of blood or packed red cells transfused. There will be analyses for the combination of autologous and allogenic transfusion and for allogenic alone.	surgery to discharge
The number of units of blood or packed red cells transfused per patient requiring transfusion.	surgery to discharge
The estimated blood loss during surgery, drainage (in milliliters) from the operative site in the first six hours post-operatively, and total drainage until removal of drains.	surgery to discharge
The change from preoperative hemoglobin concentration to postoperative hemoglobin concentration (obtained in the morning of postoperative Day 2, or, if transfused earlier, prior to transfusion	pre-operative through day 2
Surgeon's assessment of the degree to which bleeding obscures his/her view of the surgical field, relative to past, similar procedures.	surgery

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: April 22, 2008
• First Submitted That Met QC Criteria: April 27, 2008
• First Posted (Estimate): April 28, 2008

Study Record Updates

• Last Update Posted (Estimate): December 30, 2014
• Last Update Submitted That Met QC Criteria: December 26, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Bloodloss; Hip replacement surgery; Transfusion requirements; Prevention of blood loss
• Additional Relevant MeSH Terms: Pathologic Processes; Intraoperative Complications; Hemorrhage; Blood Loss, Surgical; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Hemostatics; Coagulants; Trypsin Inhibitors; Aprotinin
• Other Study ID Numbers: 11694