Tranexamic Acid During Radical Cystectomy Does Not Lead to Blood Transfusion Reduction in Bladder Cancer

The use of prophylactic tranexamic acid did not lead to a reduction in blood transfusion for patients undergoing open radical cystectomy for their bladder cancer. Due to these findings, routine use of tranexamic acid during open radical cystectomy is not recommended, according to findings from a randomized clinical trial published in JAMA Surgery.

“In this multicenter randomized clinical trial, we did not observe a benefit of prophylactic tranexamic acid in reducing red blood cell transfusion in patients undergoing open radical cystectomy for bladder cancer,” study authors wrote in their reports. “We also did not see an increased risk of venous thromboembolism or adverse perioperative outcomes with the use of prophylactic tranexamic acid ... [leading] us to conclude that prophylactic tranexamic acid is unlikely to meaningfully decrease transfusion risk in this population.”

Tranexamic acid is a lysine analogue that inhibits fibrinolysis, ultimately reducing blood loss and red blood cell transfusion during cardiac and orthopedic procedures.

Notably, patients requiring open radical cystectomy have the highest risk of red blood cell transfusion, causing investigators to hypothesize that similar effects of prophylactic tranexamic acid would be observed during radical cystectomy. This led authors to investigate if prophylactic tranexamic acid, when administered before incision and for the duration of radical cystectomy, reduces the number of red blood cell transfusions up to 30 days after surgery.

To evaluate this hypothesis, investigators conducted the Tranexamic Acid During Cystectomy Trial (TACT), a double-blind, placebo-controlled, randomized clinical trial that enrolled patients between June 2013 and January 2021. The study was conducted across 10 participating Canadian academic centers and patients were considered to be eligible for enrollment if they had a planned open radical cystectomy for the treatment of bladder cancer. Prior to randomization but after enrollment, patient demographic and disease characteristics were recorded.

Patients enrolled onto the study in the intervention arm received a loading dose of intravenous prophylactic tranexamic acid at 10 milligrams/kilogram prior to incision, followed by a maintenance infusion of 5 milligrams/kilogram per hour for the duration of the surgery and was stopped 20 minutes prior to skin closure; however, In the control arm, patients received an indistinguishable matching placebo infusion of 0.9% sodium chloride following the same volume infusion and schedule. The primary outcome of the study was receipt of red blood cell transfusion up to 30 days after surgery.

In total, 386 patients were assessed for eligibility; 33 of these patients did not meet eligibility, totaling 353 patients who were deemed eligible for evaluation, and 344 were included in the intention-to-treat analysis. These patients had a median age of 69 years and a majority were male. A total of 173 patients were randomly assigned to the investigational group and 171 were randomly assigned to the placebo group.

In patients treated with prophylactic tranexamic acid, red blood cell transfusion up to 30 days occurred in 37%, or 64, patients compared with 37.4% in the placebo-treated group. It was also reported there were no differences among the two groups in mean number of red blood cell units transfused, estimated blood loss, intraoperative transfusion or venous thromboembolic events, all of which were secondary outcomes.

There were no differences in arterial thrombotic events or venous thromboembolism. No seizures or intraoperative anaphylactic reactions were recorded, and non–transfusion-related adverse events were similar between groups. However, on the investigational arm, four patients died within 30 days, and on the placebo arm, this number was one. The primary causes were cardiac arrest, bowel perforation/sepsis, and small-intestine anastomotic leak/sepsis in the investigational group and pulmonary aspiration in the placebo group. These deaths were not believed to be attributable to the study drug, reportedly.

“Reasons for absence of benefit are unclear and may be due to patient factors, surgical factors or coadministration of intraoperative anticoagulants. Evaluation of specific surgical subgroups from completed or ongoing trials may help characterize patients who are most and least likely to benefit from prophylactic tranexamic acid administration during surgery. Based on our trial, we cannot recommend routine use of prophylactic tranexamic acid during open radical cystectomy,” study authors concluded.

Reference

“Tranexamic Acid During Radical Cystectomy: A Randomized Clinical Trial” by Dr. Rodney H. Breau, et al., JAMA Surgery.

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