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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Blood Loss, Surgical, Postoperative Hemorrhage

Intervention / Treatment
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* Drug: Trasylol (Aprotinin, BAYA0128)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Trasylol (Aprotinin, BAYA0128)<br>* 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.<br>|
| Placebo Comparator: Arm 2<br> | Drug: Placebo<br>* Placebo is used according to the description of Arm 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention of blood loss, Blood Loss, Surgical, Blood Loss, Postoperative