A randomized, double-blind, placebo-controlled, non-inferiority trial is currently being conducted across three tertiary university hospitals in Seoul, South Korea, to evaluate the efficacy of ROTEM (rotational thromboelastometry)-guided tranexamic acid (TXA) administration compared to preemptive TXA administration in reducing postoperative bleeding in patients undergoing elective cardiovascular surgery. The trial, which began in August 2023 and is expected to conclude in December 2024, seeks to determine if a ROTEM-guided approach is non-inferior to the standard preemptive TXA administration.
Trial Design and Objectives
The study is designed as a pragmatic, multi-center trial involving adult patients scheduled for elective cardiovascular surgery. Participants are randomized in a 1:1 ratio to either the ROTEM-guided TXA group (Group-GDT) or the preemptive TXA group (Group-P). The primary outcome is the amount of postoperative bleeding collected in the chest drainage during the first 24 hours after surgery. Secondary outcomes include the incidence and total amounts of intraoperative and postoperative allogeneic blood transfusions (packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate), the amount of intraoperative salvaged blood, postoperative nadir hemoglobin value, reoperation due to bleeding, and perioperative coagulation profiles.
Intervention Protocols
In Group-P, patients receive a bolus of TXA (0.5 ml/kg) after anesthesia induction, followed by a continuous infusion (0.1 ml/kg/h) until the end of the infusion. In Group-GDT, the ROTEM test is performed at multiple time points during the surgery. If the EXTEM amplitude at 10 minutes (A10-EXTEM) is ≥ 40 mm and lysis within 60 minutes in EXTEM assay (LI60-EXTEM) is ≥ 85%, patients receive a placebo. If A10-EXTEM is < 40 mm or LI60-EXTEM is < 85%, patients receive TXA. Open-label TXA administration is permitted at the discretion of the attending anesthesiologist in cases of diffuse oozing or massive bleeding.
Rationale for TXA Dosage
The trial employs a low dose of TXA (total 20 mg/kg) in Group-GDT, aligning with recent evidence suggesting that lower doses are sufficient to reduce postoperative blood loss and may be associated with a decreased incidence of seizures compared to higher doses. Group-P receives a modified low-dose regimen comprising TXA 10 mg/kg and infusion (2mg/kg/hr).
Statistical Considerations
The trial aims to enroll 764 patients to achieve 80% power, with a non-inferiority margin of 100 ml for postoperative bleeding. Statistical analyses will be performed on an intention-to-treat basis, with secondary analyses conducted on as-treated and per-protocol populations. Missing data will be handled using multiple imputation methods.
Safety Measures
Adverse events and serious adverse events (SAEs) are closely monitored and reported to the data and safety monitoring boards (DSMB) and the institutional review boards (IRB). Participants who suffer any harm will be compensated by the contracted insurance company.
