Outcome impact of different tranexamic acid regimens in cardiac surgery with cardiopulmonary bypass (OPTIMAL): Rationale, design, and study protocol of a multicenter randomized controlled trial

Tranexamic acid (TxA) reduces perioperative blood transfusion in cardiac surgery; however, the optimal dose of TxA remains unknown. This large-scale, double-blind, randomized controlled trial with a 1-year follow-up enrolls patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients are randomly assigned 1:1 into either the high-dose TxA group (intravenous bolus [30 mg/kg] after anesthesia followed by intravenous maintenance [16 mg/kg/h] throughout the operation, and a pump prime dose of 2 mg/kg) or the low-dose TxA group (intravenous bolus and maintenance are 10 mg/kg and 2 mg/kg/h, respectively, and a pump prime dose of 1 mg/kg). The primary efficacy end point is the rate of perioperative allogeneic red blood cell (RBC) transfusion defined as the number (%) of patients who will receive at least 1 RBC unit from operation day to discharge. The primary safety end point is the 30-day rate of the composite of perioperative seizures, renal dysfunction, myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary embolism, and all-cause mortality. The secondary end points are perioperative allogeneic RBC transfusion volume, the non-RBC blood transfusion rate, postoperative bleeding, reoperation rate, mechanical ventilation duration, intensive care unit stay, hospital length of stay, total hospitalization cost, each component of composite primary safety end point, and the 6-month/1-year follow-up mortality and morbidity. We estimated a sample size of 3,008 participants. The study is designed to identify a TxA dose with maximal efficacy and minimal complications. We hypothesize that the high dose has superior efficacy and noninferior safety to the low dose.