ATLANTA – Topical tranexamic acid (TxA) did not reduce the risk of seizure – and increased the risk of blood transfusion – compared with standard intravenous TxA in patients undergoing cardiac surgery, new randomized trial results show. Andre Lamy, MD, MSc, of the Population Health Research Institute, Hamilton, Ontario, presented these findings Monday during a Late-Breaking Clinical Trials session at the American College of Cardiology (ACC) Scientific Sessions 2024. Perioperative bleeding in cardiac surgery is associated with increased risk of morbidity and mortality. The standard-of-care treatment is intravenous tranexamic acid (TxA), but this increases the risk of seizure. In attempt to mitigate this risk, anesthesiologists lower the dose of TxA, but doing so could increase bleeding risk. Topical TxA on the source of bleeding showed promise in a pilot study. The question remains, though, as to whether intrapericardial topical TxA reduces the risk of in-hospital seizure, without increasing the need for red blood cell transfusion, as compared with standard intravenous TxA administration. The investigator-initiated DEPOSITION randomized trial, funded by the Canadian Institute of Health Research, included a double dummy to maintain blinding, meaning that every patient received two syringes of up to 10 g for intravenous use and two syringes of up to 10 g for topical use. Inclusion criteria included patients 18 years or older undergoing cardiac surgery with cardiopulmonary bypass and median sternotomy. Exclusion criteria included too low or too high of bleeding risk, minimally invasive surgery or off-pump coronary artery bypass grafting, bleeding disorder, estimated glomerular filtration rate <30 mL/min, preoperative hemoglobin >170 g/L or <110 g/L or thrombocytopenia, expected circulatory arrest, and active endocarditis. Patients were randomized to receive a 1-10 g intravenous bolus or placebo at the start of and during surgery and a 1-10 g topical bolus or placebo at the end of surgery. Patients were followed up until discharge or 10 days, whichever occurred first. The primary outcome was seizure. The secondary outcome was red blood cell transfusion. Tertiary outcomes included blood products transfusion; the composite of death, myocardial infarction or stroke; reoperation for bleeding or tamponade; and length of stay in the intensive care unit. The study investigators hypothesized that topical TxA would be superior to intravenous TxA in terms of seizure, and this was tested with Fisher’s exact with a two-sided p<0.05. The secondary outcome hypothesis was that topical TxA would be noninferior to intravenous TxA for red blood cell transfusion. To meet this standard, the upper bound of the one-sided 97.5% confidence interval (CI) needed to be <1.15, using a one-sided p<0.025. The data safety monitoring board performed a second prespecified interim analysis, at 75% enrollment of the planned 3,800 patients, and recommended that the trial be stopped for safety reasons. At this point, the trial had enrolled 3,242 patients, with 1,624 in the topical TxA arm and 1,618 in the standard arm. These patients were in 16 centers in six countries. At baseline, the patients’ mean age was 66.3 years in the topical arm and 65.7 years in the standard arm, and about three-quarters of the patients were male (77% topical and 78% intravenous). Most patients underwent isolated CABG (69% topical, 70% intravenous). Cardiopulmonary bypass time was similar between the groups (88.7 min topical, 88.6 mins intravenous), as was cross-clamp time (66.2 min vs. 66.0 min). In both groups, 96.5% of patients received the active treatment to which they were assigned, and follow-up was completed in all participants. The primary outcome showed a lower rate, which just missed statistical significance, of seizure (excluding patients who experienced stroke) in the topical group (n=4, 0.2%) compared to the intravenous group (n=11, 0.7%; risk ratio [RR]: 0.36 [95% CI: 0.12-1.14]; p=0.07). The secondary outcome showed a significantly higher rate of red blood cell transfusion in the topical group (35.1%) than in the intravenous group (26.8%; RR: 1.31 [95% CI: 1.18-1.46]; p<0.001) “The signal for harm with topical administration for increased blood transfusions was clearly significant,” Lamy said in a news release. “Topical administration in its current form is inferior to intravenous TxA and should not be used.” Photo Credit: Jason Wermers/CRTonline.org Photo Caption: Andre Lamy, MD, MSc, presents results from the DEPOSITION trial Monday at ACC.24 in Atlanta.