Brief Title: Tranexamic Acid During Cystectomy Trial (TACT)

INTRODUCTION

• Org Study ID: CIHR MOP-342559
• Secondary ID: Control # 162042
• NCT ID: NCT01869413
• Sponsor: Ottawa Hospital Research Institute

BRIEF SUMMARY

A cystectomy is the removal of the bladder and adjacent organs in patients with bladder
cancer. This often results in significant blood loss, and about 60% of patients will require
a blood transfusion during or up to 30 days after surgery. Significant blood loss may result
in cardiovascular morbidity, and the use of blood products are expensive and expose patients
to risk.

Tranexamic acid reduces breakdown of hemostatic blood clots and it has therapeutic benefit
when used in other surgical procedures to reduce blood loss and the need for transfusion. The
current study will be the first to evaluate whether tranexamic acid is effective and safe to
use during radical cystectomy. The results of the study will have an immediate impact on
patient care.

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DETAILED DESCRIPTION

Removal of the bladder and adjacent organs in patients with bladder cancer (radical
cystectomy) often results in significant blood loss, and approximately 60% of patients
require peri-operative blood transfusion. Reducing blood loss and the frequency of
transfusion offers several benefits, including donor blood conservation, health care cost
reduction, and avoidance of blood product exposure. Tranexamic acid is an amino acid lysine
derivative with strong antifibrinolytic clotting properties that can be administered
systemically. This medication has been used in a variety of operative procedures, notably in
high risk cardiac surgery, to decrease peri-operative blood loss, and it is associated with
an acceptable risk of adverse events. Systemic anti-hemorrhagics are infrequently used during
radical cystectomy, and to the investigators knowledge their effects have not been evaluated
in a clinical trial.

Overall objective: To conduct a randomized controlled trial of systemic tranexamic acid
compared to placebo in reducing the number of blood transfusions in patients undergoing
radical cystectomy for bladder cancer.

Design: A multi-center, randomized, double-blinded, placebo controlled trial.

Study population: Consenting patients 18 years of age and older undergoing a radical
cystectomy for bladder cancer, excluding those who: are unwilling to receive blood products
due to personal reasons, are pregnant, have active angina, have a known allergy to tranexamic
acid, or have a known personal history of deep venous thrombosis, atrial fibrillation,
coronary stent, sub-arachnoid hemorrhage, pulmonary embolism, thrombotic stroke and / or
acquired disturbance of colour vision. The study will recruit 354 patients from Dalhousie
University, McGill University, Université de Montreal, Université Laval, University of
Ottawa, University of Western Ontario and University of Alberta.

Intervention:

Tranexamic Acid arm: Tranexamic acid will be administered as an intravenous infusion of 10
mg/kg within 10 minutes (loading dose) and before surgical incision, followed by 5 mg/kg/hour
continuous maintenance infusion for the length of surgery (typically 4 to 8 hours). For
example, an 80 kg patient would receive 800 mg prior to incision and a 400 mg/hour infusion
for the duration of surgery. For a 6 hour procedure, the total dose administered would be
3200 mg.

Placebo arm: As there is no standard of care concerning administration of antifibrinolytic
agents in cystectomy procedures, controls will follow the same dosing and schedule described
above, but with 0.9% saline infusion.

Outcomes: The primary research objective is whether the use of systemic tranexamic acid
compared to placebo reduces the proportion of radical cystectomy patients requiring red blood
cell transfusion up to 30 days post-operative (from a 50% transfusion rate with placebo to
35% with tranexamic acid). Secondary questions are: Will use of systemic tranexamic acid
compared to placebo result in reductions in: i) intraoperative blood loss, ii) amounts of
transfused blood products, and iii) post-operative complications? The safety (thrombotic
events) of tranexamic acid will also be evaluated.

Importance of this study: If tranexamic acid reduces the number of blood transfusions, there
will be an immediate impact to cystectomy patients, and surgeons may consider the routine use
of systemic tranexamic acid during similar abdomino-pelvic procedures associated with
significant blood loss.

• Overall Status
  Recruiting
• Start Date
  
• Phase
  Phase 2/Phase 3
• Study Type
  Interventional