Trial Information

Tranexamic Acid During Cystectomy Trial (TACT) Pilot Study

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 an internal pilot study to determine feasibility of 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: An internal pilot study, employing the protocol of the full 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 pilot study will recruit the
first 55 patients of 354 patients required for the full study 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 over 10 minutes (loading dose) 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 principal research questions for the investigators internal pilot (current
application) pertain to feasibility of enrollment of cystectomy patients using the full RCT
protocol of tranexamic acid vs. placebo. The pilot will address feasibility of site-specific
enrollment, feasibility of multiple site start-ups, and feasibility of institutional ethics
approval, protocol administration, and multicenter coordination.

The primary research objective for the investigators full RCT 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 for the investigators
full trial 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: A successful pilot will encourage us to continue with the full RCT
that will determine whether tranexamic acid reduces blood loss and subsequent transfusions
during radical cystectomy. 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.