Brett L. Houston, Daniel I. McIsaac, Rodney H. Breau, Salmaan Kanji, Peter Greenstreet, Meghan Andrews, Sinziana Avramescu, Hema Bagry, R Balshaw, Jayesh Daya, Kaitlin Duncan, Christopher Harle, Eric Jacobsohn, Tina Kerelska, M Pitz, Paul Komenda, Sarah McIsaac, Tim Ramsay, Tarit Saha, Alan Tinmouth, Angela Recio, Daniel Szoke, Marshall Tenenbein, Sarah Slagerman, Dayna Solvason, Robert Talarico, Dean A. Fergusson, Ryan Zarychanski
BACKGROUND: Whether a hospital policy of tranexamic acid administration for patients undergoing major noncardiac surgery safely reduces the need for red-cell transfusion is uncertain. METHODS: We conducted a multicenter, double-blind, cluster-randomized, placebo-controlled trial involving patients undergoing noncardiac surgery who were at high risk for red-cell transfusion. Hospitals were randomly assigned at 4-week intervals to a hospital-wide policy of intraoperative tranexamic acid or placebo. The coprimary effectiveness and safety outcomes were transfusion of red cells during the index hospitalization and diagnosis of venous thromboembolism within 90 days, respectively. The safety outcome was assessed for noninferiority, with a prespecified noninferiority margin defined as an upper boundary of 1.46 for the 95% confidence interval of the relative risk. Analyses used mixed-effects models that accounted for the cluster-crossover design. RESULTS: A total of 8273 patients enrolled across 10 Canadian hospitals could be evaluated for the coprimary outcomes. Oncologic surgery accounted for 60.5% of the surgical procedures (5002 of 8273). The percentage of patients who received a red-cell transfusion during hospitalization was 7.4% (306 of 4156) in the tranexamic acid group and 9.8% (403 of 4117) in the placebo group (relative risk, 0.73; 95% confidence interval [CI], 0.61 to 0.86; adjusted difference, -2.7 percentage points; 95% CI, -4.2 to -1.4). Venous thromboembolism within 90 days occurred in 2.1% of patients (86 of 4128) in the tranexamic acid group and 2.1% of patients (85 of 4052) in the placebo group (relative risk, 0.96; 95% CI, 0.65 to 1.38; adjusted difference, -0.1 percentage points; 95% CI, -0.9 to 0.7), which met the criterion for noninferiority. CONCLUSIONS: Among patients undergoing major noncardiac surgery, a hospital policy of tranexamic acid administration resulted in a lower incidence of red-cell transfusion than placebo administration, and tranexamic acid was noninferior to placebo with regard to diagnosis of venous thromboembolism. (Funded by the Canadian Institutes of Health Research and others; TRACTION ClinicalTrials.gov number, NCT04803747.).