Coronary Artery Disease, Perioperative Bleeding
Conditions
Keywords
Tranexamic Acid, Off-Pump Coronary Artery Bypass Grafting, OPCAB, Oral Administration, Intravenous Administration, Postoperative Blood Loss, Cardiac Surgery, Non-Inferiority Trial
Brief summary
Tranexamic acid is commonly administered intravenously during cardiac surgery to reduce perioperative bleeding. Oral tranexamic acid may offer a simpler and less costly alternative, but its effectiveness in patients undergoing off-pump coronary artery bypass grafting has not been adequately established. TRANSCAB is a randomized, double-blind, parallel-group, non-inferiority clinical trial comparing oral and intravenous tranexamic acid in adults undergoing elective off-pump coronary artery bypass grafting. Participants will receive either oral tranexamic acid before surgery with an intravenous placebo at induction, or oral placebo before surgery with intravenous tranexamic acid at induction. The primary objective is to determine whether oral tranexamic acid is non-inferior to intravenous tranexamic acid for reducing postoperative blood loss. Secondary objectives include comparing transfusion requirements, postoperative hemoglobin levels, reoperation for bleeding, thromboembolic complications, seizures, acute kidney injury, and other postoperative outcomes.
Detailed description
Perioperative bleeding remains an important complication of coronary artery bypass surgery and may lead to blood transfusion, reoperation, prolonged hospitalization, and increased postoperative morbidity. Tranexamic acid is an antifibrinolytic drug widely used in cardiac surgery to reduce bleeding and transfusion requirements. It is most commonly administered intravenously, although oral administration may provide adequate systemic exposure while simplifying drug preparation and administration. TRANSCAB is a monocentric, prospective, randomized, double-blind, placebo-controlled, parallel-group, non-inferiority trial conducted in adult patients undergoing elective off-pump coronary artery bypass grafting. A total of 160 participants will be randomized in a 1:1 ratio to one of two treatment groups: 1. Oral tranexamic acid group: four 500 mg tranexamic acid tablets administered approximately 2 hours before surgical incision, together with an intravenous placebo administered at induction or incision according to the study protocol. 2. Intravenous tranexamic acid group: four matching oral placebo tablets administered approximately 2 hours before surgical incision, together with 1 g intravenous tranexamic acid administered at induction or incision according to the study protocol. Participants, clinicians involved in perioperative management, outcome assessors, and investigators will remain blinded to treatment allocation. Study treatments will be prepared and dispensed according to the randomization list by the hospital pharmacy. The primary objective is to assess whether oral tranexamic acid is non-inferior to intravenous tranexamic acid in reducing postoperative blood loss following off-pump coronary artery bypass grafting. Secondary and safety outcomes will assess perioperative transfusion requirements, postoperative hemoglobin changes, clinically significant bleeding, reoperation for bleeding, thromboembolic events, seizures, acute kidney injury, mortality, duration of intensive care and hospital stay, and other postoperative complications specified in the protocol.
Interventions
Tranexamic acid, 2 g orally, administered as four 500 mg tablets approximately 2 hours before surgical incision.
DRUGExacyl®
Tranexamic acid, 1 g intravenously, diluted in 0.9% sodium chloride to a total volume of 50 mL and administered at induction or incision according to the study protocol.
DRUGIntravenous placebo
Intravenous placebo consisting of 50 mL of 0.9% sodium chloride, administered at induction or incision according to the study protocol.
Sponsors
Clinique Saint-Luc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A double-dummy design is used. Participants receive either oral tranexamic acid and intravenous placebo or oral placebo and intravenous tranexamic acid. Participants, perioperative care providers, investigators, and outcome assessors are unaware of treatment allocation. The randomization list is held by the hospital pharmacy, with emergency unblinding available according to the protocol.
Intervention model description
Participants are randomized in a 1:1 ratio to two parallel groups comparing oral tranexamic acid with intravenous tranexamic acid using a double-dummy design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. Elective isolated coronary artery bypass grafting planned without cardiopulmonary bypass, including off-pump coronary artery bypass through sternotomy or minimally invasive/direct or totally endoscopic coronary artery bypass surgery. Conversion to cardiopulmonary bypass is permitted if clinically required. 3. Perioperative tranexamic acid planned as part of routine care, with the participant eligible for both oral and intravenous administration according to the applicable product information and local policy. 4. Written informed consent obtained before randomization. 5. Routine preoperative laboratory results available, including at least hemoglobin and serum creatinine measured within 30 days before surgery. 6. Available for in-hospital follow-up and Day 30 assessment.
Exclusion criteria
1. Emergency surgery, non-isolated cardiac surgery, or planned on-pump coronary artery bypass grafting. 2. Inability to provide informed consent or comply with the required follow-up. 3. Hypersensitivity to tranexamic acid or any excipient of the study products. 4. Contraindication or clinically relevant precaution to tranexamic acid according to the applicable product information, including: * active arterial or venous thromboembolic disease or active intravascular clotting; * history of subarachnoid hemorrhage; * acquired defective color vision; * clinically relevant seizure disorder or previous tranexamic-acid-associated seizure; * disseminated intravascular coagulation without predominant hyperfibrinolysis; * active upper urinary tract hematuria with a risk of ureteric obstruction. 5. Renal function incompatible with the fixed protocol dose, including estimated glomerular filtration rate below 30 mL/min/1.73 m² or dialysis. 6. Contraindication to either administration route, including inability to swallow tablets, malabsorption precluding oral dosing, or inability to obtain intravenous access. 7. Pregnancy or breastfeeding. 8. Participation in another interventional clinical trial that could interfere with study outcomes or safety. 9. Planned use of another antifibrinolytic agent outside the protocol, including aprotinin or epsilon-aminocaproic acid. 10. Any new clinical condition identified after randomization but before dosing that, in the investigator's judgment, makes administration of the study treatment unsafe. 11. Uncontrolled hemodynamic or respiratory instability before administration of the study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Chest Tube Blood Loss Within 24 Hours After Surgery (mL) | From completion of surgery to 24 hours postoperatively | Total cumulative volume of blood collected from mediastinal and pleural chest drains during the first 24 hours after completion of surgery, expressed in milliliters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Receiving Red Blood Cell Transfusion | From surgery until hospital discharge, up to 30 days | Number and proportion of participants receiving at least one unit of packed red blood cells during surgery or the postoperative hospital stay, and the total number of units transfused per participant. |
| Hemoglobin Concentration at 24 Hours After Surgery (g/dL) | At 24 hours after surgery | Hemoglobin concentration measured from routine postoperative blood samples, expressed in grams per deciliter. |
| Number of Participants Requiring Reoperation for Bleeding | During the index hospitalization, up to 30 days | Number and proportion of participants requiring surgical re-exploration because of postoperative bleeding or cardiac tamponade. |
| Number of Participants With Thromboembolic Events | From study intervention until 30 days after surgery | Occurrence of clinically diagnosed arterial or venous thromboembolic events, including myocardial infarction, ischemic stroke, deep vein thrombosis, or pulmonary embolism. |
| Number of Participants With Postoperative Seizures | During the index hospitalization, up to 30 days | Occurrence of clinically diagnosed postoperative seizures. |
| Number of Participants With Acute Kidney Injury According to Kidney Disease: Improving Global Outcomes (KDIGO) Criteria | Within 7 days after surgery or until hospital discharge, whichever occurs first | Number of participants with postoperative acute kidney injury classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria (Stages 1, 2, or 3). |
| Number of Participants With All-Cause Mortality Within 30 Days After Surgery | Within 30 days after surgery | Death from any cause. |
| Length of Intensive Care Unit Stay (days) | From intensive care unit admission until discharge from the intensive care unit, up to 30 days | Duration of the postoperative intensive care unit stay, expressed in hours or days. |
| Length of Hospital Stay (days) | From the date of surgery until hospital discharge, up to 30 days | Duration of the postoperative hospital stay, expressed in days. |
Countries
Belgium
Contacts
CONTACTBenjamin Javillier, MD
PRINCIPAL_INVESTIGATORBenjamin Javillier, MD
Clinique Saint-Luc Bouge
Outcome results
None listed