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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-004055-35-SE
• Date of registration: 21/12/2005
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 17/01/2006
• Target sample size: 278
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004055-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Germany, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects (men or non-pregnant women) 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 surgery; if no records are available, or if the subject received aprotinin, the subject should be excluded)
Subjects with known or suspected allergy to aprotinin
Subjects undergoing laparoscopic surgery.
Patients with symptoms indicative for sepsis or local urinary tract infections that make the patient inlegible for total or radical cystectomy
Subjects with impaired renal function (serum creatinine of >2.5 mg/dL or 221 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
Subjects whose preoperative RBC volume is so low that blood will have to be given peri-operatively (Hct or Hgb values <24% or <8 g/dL, respectively)
Subjects with a history of Deep Vein Thrombosis or Pulmonary Embolism
Subjects who are pregnant 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 (Amicar®) or tranexamic acid (Cyklokapron®)
Subjects on chronic anticoagulant treatment with warfarin where it cannot be discontinued for the surgical procedure
Subjects on an investigational drug (i.e. not marketed) in the 30 days prior to screening or during the trial before the 6 week follow-up visit. Subjects involved in trials of marketed cancer therapy medications (including those approved for another indication) or combination with radiotherapy are allowed.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Radical or total cystectomy on patients with bladder cancer

Intervention(s)

Product Name: Trasylol
Product Code: Bay a 0128
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: aprotinin
Other descriptive name: serine protease inhibitor
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 10000-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective:

Main Objective: Main objective: The objective of this study is to evaluate the safety and efficacy of aprotinin as compared to placebo, in reducing the need for subsequent blood transfusion in subjects with bladder cancer undergoing to radical or total cystectomy. The undermentioned procedures are allowed and belong to radical and total cystectomy: 1 Total cystectomy 2. radical cystectomy procedures = cystectomy plus removal of adjacent tissues:Cystoprostatectomy, Removal of bladder and anterior vaginal wall, Cystectomy plus ovariectomy and or hysterectomy 3. Urinary tract reconstructive procedures: Type of urinary tract reconstruction, like Bricker procedure, neo bladder from jejunum

Primary end point(s): The objective of this study is to evaluate the safety and efficacy of aprotinin as compared to placebo, in reducing the need for subsequent blood transfusion in subjects with bladder cancer undergoing to radical or total cystectomy. 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). The primary analysis will be based on all patients undergoing protocol defined surgery that are valid for analysis of intent to treat.
Secondary end points:
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.
The number of units of blood or packed red cells transfused per patient requiring transfusion.
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.
The drainage volume (in milliliters) from the operative site in the first 8 hours post-operatively, and daily total drainage until removal of drains.
Transfusion of platelets, colloids, plasma and number of patients requiring these products
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.
Changes in blood markers related to inflammation and blood coagulation
Time to discontinuing of mechanical ventilation
Changes in FEV1
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.
In addition, exploratory analyses might be performed to determine the influence of factors known to affect blood loss (i.e., ASA/NSAID use, EPO use, concomitant medication use for DVT prophylaxis, and type of anesthesia) on the estimate of treatment effect. Also, changes in plasma urokinase plasminogen activator (uPA) will be exploratory.
Health Economics and Outcomes variables will include:
Prior to the surgery: Preoperative blood donation.
In the intra-operative and postoperative period (up to discharge): Duration of surgery; Duration of Intensive Care Unit (ICU) stay post operation, Duration of recovery room stay post operation; Anti-infective medications, prophylactic and/or treatment for postoperative infection (wound infection and other infections); Length of hospital stay (from the date of surgery to the date of discharge); Cost of hospital stay (total cost and all itemized costs including cost of blood transfusion, autologous or allogenic-blood products, administration, and equipment; cost data will only be collected from applicable sites).
A follow-up questionnaire will be administered to study subjects to collect the following information within the post discharge period: Number of office visit(s), Number of emergency room visit(s), Number and duration of hospitalization(s), Whether patient had an infection.
The analyses of cost data will be outlined in the statistical analysis plan (SAP) before unblinding of the study. The Health Economics outcome results will be an addendum to the MRR.

Overall survival up to 2 years
An exploratory analysis of the overall survival will be performed based on data collected during the 2 year follow-up (by phone call every 3 months). Sub-analysis of survival data and the other secondary endpoints based on type of cancer and high plasma uPA at baseline will be performed. This data analysis will be performed after database lock for the primary and secondary analyses that will be closed after the 6 ± 2 week follow up visit. The survival data will not form part of the final MRR but will be included as an addendum to this document.
A blood sample will be drawn to measure baseline aprotinin antibodies. This results will only be used to develop an assay that may be able to identify patients who have increased risk for developing hypersensitivity reaction to Trasylol. This assay is early in its development and it has not been nor will be used clinically to identify those individual risks.

Secondary ID(s)

2005-004055-35-DE

Bay a 0128/12002