Efficacy and Safety of Aprotinin on Transfusion Requirements in Patients Undergoing Radical or Total Cystectomy

A Multi-center, Randomized, Double Blind, Placebo Controlled Study to Investigate the Efficacy and Safety of Aprotinin on Transfusion Requirements in Patients With Bladder Cancer Undergoing Radical or Total Cystectomy.

The purpose of this study is to assess if aprotinin (BAYA0128), given intravenously during your surgery, is safe and can help reduce the need for a blood transfusion during bladder surgery.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
  • Leuven, Belgium, 3000
• France
  • Nantes Cedex, France, 44035
  • Nice, France, 06200
• Germany
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
  • Bayern
    • München, Bayern, Germany, 81377
    • Regensburg, Bayern, Germany, 93053
  • Hessen
    • Fulda, Hessen, Germany, 36043
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Saarland
    • Homburg, Saarland, Germany, 66421
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
• Netherlands
  • Maastricht, Netherlands, 6229 HX
  • Nijmegen, Netherlands, 6525 GA
• Sweden
  • Linköping, Sweden, 581 85
  • Lund, Sweden, 221 85
  • Stockholm, Sweden, 171 76
  • Uppsala, Sweden, 751 85
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
  • Tyne and Wear
    • Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
• United States
  • California
    • Los Angeles, California, United States, 90095
  • Colorado
    • Denver, Colorado, United States, 80262
  • Florida
    • Miami, Florida, United States, 33125
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Chicago, Illinois, United States, 60612
  • Maine
    • Portland, Maine, United States, 04102
  • Maryland
    • Baltimore, Maryland, United States, 21224
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0330
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7065
  • Ohio
    • Cleveland, Ohio, United States, 44106-2602
    • Columbus, Ohio, United States, 43214-1419
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
    • Pittsburgh, Pennsylvania, United States, 15213-2592
  • Tennessee
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Houston, Texas, United States, 77030
  • Vermont
    • Burlington, Vermont, United States, 05401-1420

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 18 years of age and older
• Subjects requiring elective radical or total cystectomy for bladder cancer
• 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 or with a known or suspected allergy to aprotinin
• Subjects with sepsis or undergoing laparoscopic surgery
• Subjects with impaired renal function (serum creatinine >2.5 mg/dL or 221 micromoles/liter)
• Subjects with a history of bleeding diathesis, deep vein thrombosis or pulmonary embolism or known coagulation factor deficiency. Based on the investigator's opinion of any active significant medical illness the subject may have
• Subjects who refuse to receive allogenic blood products or whose preoperative red blood cell volume is so low that a blood transfusion would be likely to be given perioperatively (preoperative hematocrit of <24% or hemoglobin of <8 g/dl)
• Subjects who have participated in an investigational drug study within the past 30 days
• Subjects who are pregnant or breastfeeding or women of childbearing potential in whom the possibility of pregnancy cannot be excluded by a negative pregnancy test and who are not using a reliable method of contraception
• Planned use of other antifibrinolytic agents, e.g. aminocaproic acid or tranexamic acid
• Subjects on chronic anticoagulant treatment with warfarin that cannot be temporarily discontinued for the surgical procedure (as per local practices)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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); Subjects will be randomized to receive an infusion of aprotinin (a test dose followed by a loading dose of 2 million KIU before skin incision followed by 500,000 KIU/hour until the end of surgery) or matching placebo. The maximal dose of aprotinin, that can be administered is 7,000,000 KIU, regardless of the duration of the operation. When a total of 7 million has been reached the administration of aprotinin must be discontinued.
Placebo Comparator: Arm 2	Drug: Placebo; Placebo is used according to the description of Arm 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary criterion for efficacy is the percent of patients requiring a blood transfusion anytime in the intra-operative or post-operative period (up to the earlier of Day 7 or discharge)	Anytime in the intra-operative or post-operative period (up to the earlier of Day 7 or discharge)

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of units of blood or packed red cells transfused. There will be an analysis for the combination of autologous and allogenic transfusion and for allogenic alone	Intra- and postoperative
The number of units of blood or packed red cells transfused per patient requiring transfusion	Intra- and postoperative
The intraoperative blood loss determined as follow: a) by surgeon estimate b) summing weight of the blood in gauze and other materials and the suction drainage volume	Intraoperative
The drainage volume (in milliliters) from the operative site	In the first 8 hours post-operatively, and daily total drainage until removal of drains or until discharge, whichever comes first
Transfusion of platelets, colloids, plasma and number of patients requiring these products	Intra- and postoperative
The change from preoperative hemoglobin concentration to postoperative hemoglobin concentration	Obtained in the morning of postoperative Day 3, or, if transfused earlier, prior to transfusion
Surgeon s assessment of the degree to which bleeding obscures his/her view of the surgical field, relative to past, similar procedures	Intraoperative
Changes in blood markers related to inflammation and blood coagulation; baseline until Discharge or day 7	Several measurements from baseline up to 6 weeks
Time to discontinuing of mechanical ventilation	Not specifed
Changes in FEV1	Baseline until Discharge or day7
Changes in the patients health related quality of life (HRQoL) (at baseline and 6+-2 weeks post surgery) using the Functional Assessment Cancer Therapy for patients with Bladder cancer (FACT-Bl) questionnaire	At baseline and 6+-2 weeks post surgery

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here and search for information of Bayer products for Europe

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: March 21, 2006
• First Submitted That Met QC Criteria: March 21, 2006
• First Posted (Estimate): March 23, 2006

Study Record Updates

• Last Update Posted (Estimate): December 17, 2014
• Last Update Submitted That Met QC Criteria: December 16, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Blood Loss, Surgical; Prevention of blood loss; Blood Loss, Postoperative
• 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: 12002 (DAIDS-ES); 2005-004055-35 (EudraCT Number)