For a study, researchers sought to evaluate the effectiveness and side effects of high-dose tranexamic acid against low-dose tranexamic acid in patients undergoing cardiopulmonary bypass.
During a multicenter, double-blind, randomized clinical study, adult patients have a cardiopulmonary bypass. Between December 26, 2018, and April 21, 2021, 3,079 participants from 4 hospitals were included in the trial. The last follow-up took place on May 21, 2021. Participants were given either a low-dose regimen of tranexamic acid, which included a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, or a 1-mg/kg/kg prime (n=1,506) or a high-dose regimen of tranexamic acid comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose (n=1,525). The primary safety endpoint was a composite of the 30-day postoperative rates of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). The primary efficacy endpoint was the rate of allogeneic red blood cell transfusion after the start of operation (superiority hypothesis). In addition to the various parts of the primary safety endpoint, there were 15 secondary endpoints.
The experiment was completed by 3,031 (98.4%) of the 3,079 patients randomly assigned to therapy groups (mean age, 52.8 years; 38.1% women). In the high-dose group, allogeneic red blood cell transfusions happened in 333 of 1,525 patients (21.8%) and in 391 of 1,506 patients (26.0%) (risk difference [RD], 4.1% [1-sided 97.55% CI, -∞ to 1.1%]; relative risk, 0.84 [1-sided 97.55% CI,-∞ to 0.96; P=.004]). Two-hundred and sixty-five patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) had the composite of postoperative seizure, thrombotic events, renal failure, and mortality (RD, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; P=.003 for noninferiority). Seizures occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, -0.0% to 1.2%; P=.05. Of the 15 prespecified secondary end goals, 14 were not substantially different between groups.
High-dose tranexamic acid infusion compared to low-dose tranexamic acid infusion resulted in a modest statistically significant decrease in the percentage of patients who required an allogeneic red blood cell transfusion and fulfilled criteria for noninferiority with regard to a composite primary safety endpoint composed of 30-day mortality, seizure, kidney dysfunction, and thrombotic events.