Effect of Aprotinin on Transfusion Requirements in Patients Undergoing Elective Spinal Fusion Surgery

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, 2-Arm Study to Investigate the Effect of Aprotinin on Transfusion Requirements in Patients Undergoing Elective Spinal Fusion Surgery

The objective of this study is to evaluate the safety and efficacy of aprotinin as compared to placebo, in reducing the need for blood transfusion in adult subjects undergoing elective spinal fusion surgery involving 3 to 7 vertebral levels with instrumentation

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
    • Windsor, Ontario, Canada, N9A 1E1
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
• Germany
  • Berlin, Germany, 13353
  • Berlin, Germany, 13086
  • Baden-Württemberg
    • Karlsbad, Baden-Württemberg, Germany, 76307
  • Nordrhein-Westfalen
    • Münster, Nordrhein-Westfalen, Germany, 48149
  • Schleswig-Holstein
    • Neustadt, Schleswig-Holstein, Germany, 23730
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28034
  • Pamplona, Spain, 31008
  • Valencia, Spain, 46010

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 spinal fusion surgery involving 3 to 7 vertebral levels with instrumentation. One vertebral level is defined as encompassing two vertebral bodies and one inter-vertebral disc space, so that a contiguous spinal fusion involving 3 vertebral levels would include 4 vertebral bodies and 3 inter-vertebral disc spaces.

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, or if the subject received aprotinin, the subject should be excluded.- Subjects with a known or suspected allergy to aprotinin.
• Subjects with sepsis or a known bone infection.- Subjects with known bone malignancy.
• Subjects with a creatinine clearance less than 30mL/min as calculated by the Cockcroft-Gault formula.
• 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.
• Subjects whose preoperative red blood cell volume is so low that a blood transfusion would be likely to be given perioperatively (preoperative hematocrit or hemoglobin values <24% or <8 g/dl, respectively).
• Subjects who have participated in an investigational drug study within the past 30 days
• Subjects with a history of deep vein thrombosis or pulmonary embolism.
• Subjects who are pregnant or breast feeding.
• Women of childbearing potential in whom the possibility of pregnancy cannot be excluded by a negative serum pregnancy test at screening.
• Women of childbearing potential who are not using a reliable method of contraception.
• Planned use of other antifibrinolytic agents.
• Subjects on chronic anticoagulant treatment with Vit K antagonists that cannot be temporarily discontinued for the surgical procedure (as per local practices).

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); Infusion of aprotinin (loading dose of 2 million KIU (Kallikrein Inhibitor Units) followed by 500,000 KIU/hour until the end of surgery)
Placebo Comparator: Arm 2	Drug: Placebo; Infusion of placebo (loading dose of 2 million KIU (Kallikrein Inhibitor Units) followed by 500,000 KIU/hour until the end of surgery)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
The percent of patients 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 patients 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
Drainage (in milliliters) from the operative site in the first 8 hours postoperatively, and total drainage until removal of drains or until hospital discharge (whichever is earlier)	surgery to discharge
Blood loss during surgery, based on qualitative and quantitative estimates	surgery
The change from preoperative hemoglobin concentration to postoperative hemoglobin concentration (obtained in the morning of Day 3, or, if transfused earlier, prior to transfusion).	pre-op and day 3 post surgery
Surgeons assessment of the degree to which bleeding obscured his/her view of the surgical field, relative to past, similar procedures	surgery to discharge
The percent of patients receiving colloid or other blood products, and the number of units transfused	surgery to discharge
Changes in blood markers related to inflammation and blood coagulation	surgery to discharge
Changes in FEV1	surgery to discharge

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2006
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: May 16, 2006
• First Submitted That Met QC Criteria: May 16, 2006
• First Posted (Estimate): May 18, 2006

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 2, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Bloodloss; Transfusion Requirements in Patients Undergoing Elective Spinal Fusion Surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Intraoperative Complications; Hemorrhage; Blood Loss, Surgical; Postoperative Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Hemostatics; Coagulants; Trypsin Inhibitors; Aprotinin
• Other Study ID Numbers: 11799; 2005-003999-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No