Study to Investigate the Effect of Aprotinin of Transfusion Requirements in Patients Undergoing Surgical Procedures for Lung or Esophageal Cancer

Study Overview
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Brief Summary
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Study to Investigate the Effect of Aprotinin of Transfusion Requirements in Patients Undergoing Surgical Procedures for Lung or Esophageal Cancer.

Official Title
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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 Surgical Procedures for Lung Cancer or Esophageal Cancer

Conditions
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Blood Loss, Surgical

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: Men or women 18 years of age and older Subjects requiring protocol specified oncological surgery. Subjects must have histological confirmation of malignancy in lung or esophagus Documented, signed and 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 undergoing laparoscopic surgery Subjects with sepsis or mesothelioma 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Trasylol (Aprotinin, BAYA0128)<br>* Subjects successfully meeting all screening criteria 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 aprotinin was supplied in infusion vials of 200mL solution containing 2,000,000 KIU (10,000 KIU/mL) in 0.9% sodium chloride. Subjects will be stratified into one of the 4 following strata: Stratum 1: complete primary pneumonectomy Stratum II: decortication or completion pneumonectomy Stratum III: esophagectomy by transhiatal approach Stratum IV: esophagectomy by transthoracic approach<br>|
| Placebo Comparator: Arm 2<br> | Drug: Placebo<br>* Placebo solution was supplied in identical vials and will consist of 200mL of 0.9% sodium chloride.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients requiring a blood transfusion anytime in the intra-operative or post-operative period |  | Up to the end of follow up visit (4 to 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of units of blood or packed red cells transfused |  | Up to the end of follow up visit (4 to 8 weeks) | 
| Number of units transfused per patient |  | Up to the end of follow up visit (4 to 8 weeks) | 
| Intra-operative blood loss |  | Intra-operative | 
| Drainage volume |  | Until removal of drains | 
| Transfusion of platelets, colloids and plasma |  | Up to the end of follow up visit (4 to 8 weeks) | 
| Change from pre-operative to post-operative hemoglobin concentration |  | At day 3 or earlyer prior to transfusion | 
| Surgeon's assessment of obscurement of operative field by bleeding |  | Up to the end of follow up visit (4 to 8 weeks) | 
| Blood markers of inflammation and coagulation |  | Up to the end of follow up visit (4 to 8 weeks) | 
| Time to discontinuation of mechanical ventilation |  | Until removal of mechanical ventilation | 
| Health related quality of life measurements |  | Up to the end of follow up visit (4 to 8 weeks) |