Bleeding, Seizures, Surgical Blood Loss
Conditions
Keywords
cardiac surgery, tranexamic acid, cardiopulmonary bypass, seizure, blood transfusion
Brief summary
The goal of this clinical trial is to establish the feasibility of conducting a large trial to determine the optimal timing of intravenous tranexamic acid administration in cardiac surgery. The main questions it aims to answer are: * Is it feasible to conduct a larger definitive trial? * Can we measure the systemic tranexamic acid concentration and fibrinolytic potential in the blood samples? Researchers will compare intravenous tranexamic acid administered before cardiopulmonary bypass versus after cardiopulmonary bypass to see if the systemic tranexamic acid concentration and fibrinolytic potential are similar or better. Participants will: * Provide written informed consent * Receive tranexamic acid during surgery * Provide blood samples at 5 time points: before surgery, on arrival in intensive care unit, 3 hours after arrival, 6 hours after arrival, and on the next morning.
Detailed description
Postoperative bleeding related to open cardiac surgery increases the rates of complications and mortality. It results from the blood thinners that are needed for use. Intravenous tranexamic acid (TxA) has become a mainstay in cardiac surgical procedures for decreasing bleeding and minimizing transfusion requirements. Although intravenous TxA is usually well tolerated, there is a well-known risk (1 to 4%) of postoperative seizures. This is due to the similarity between TxA and the brain tissues. The aim is to eliminate the risk of seizures and to improve the protection against bleeding. When TxA is used before and during cardiopulmonary bypass (CPB), the presence of systemic TxA during de-airing of the heart and the termination of CPB may facilitate entry of TxA into the brain causing seizures. Administration of TxA after CPB may result in higher systemic concentrations that may be more effective for protecting against bleeding after surgery. The aim is to establish the feasibility of a definitive trial to prove that administration of TxA after CPB can eliminate postoperative seizures and reduce the amount of blood transfusions in patients who have cardiac surgery.
Interventions
DRUGBefore CPB Tranexamic Acid
Tranexamic acid 1 to 10 g (10 to 100 mL) administered intravenously as per standard care at the induction of anesthesia as a bolus and/or continuous infusion (i.e., before CPB).
DRUGAfter CPB Tranexamic Acid
Tranexamic acid 5 g (50 mL) administered after heparin reversal (i.e., after CPB).
DRUGBefore CPB Placebo
Placebo (10 to 100 mL saline) administered intravenously at the induction of anesthesia as a bolus and/or continuous infusion.
DRUGAfter CPB Placebo
Placebo (50 mL saline) administered after heparin reversal.
Sponsors
Hamilton Health Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
After CPB Tranexamic Acid + Before CPB Placebo versus Before CPB Tranexamic Acid + After CPB Placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. ≥18 years of age 2. Undergoing a cardiac surgical procedure (i.e., isolated CABG, isolated single cardiac valve surgery or a combination of both or isolated ascending aorta replacement) with the use of cardiopulmonary bypass 3. Provide written informed consent
Exclusion criteria
1. Allergy to tranexamic acid 2. Fulfill any of the following transfusion risk factors (A-F): A. Emergency surgery B. History of bleeding disorder C. Inherited thromboembolic or hemorrhagic disease D. Infective endocarditis (active) E. Pre-operative thrombocytopenia (<50,000 platelets per µL) F. Pre-operative hemoglobin <110 g/L 3. Estimated glomerular filtration rate <30 mL/min (CKD-EPI equation) or on dialysis 4. Pre-operative hemoglobin >170 g/L 5. Expected circulatory arrest 6. Pregnancy or breast feeding 7. Previous enrollment in DEPOSITION trial 8. Refusal of blood products (e.g., Jehovah's Witnesses) 9. Isolated Pericardiectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure the level of plasma TxA at 5 time points | From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. | Measure the level of plasma TxA at 5 time points: pre-operative, on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points | From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. | Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points: pre-operative baseline, on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. |
| Measure the plasmin generation (i.e., fibrinolytic activity) at 5 time points | From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. | Measure the plasmin generation (i.e., fibrinolytic activity) at 5 time points: pre-operative baseline, on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients experiencing an in-hospital seizure | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Appropriate descriptive statistics will be provided. |
| Proportion of patients requiring any blood product transfusion | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Appropriate descriptive statistics will be provided. |
| Proportion of patients requiring re-operation for bleeding or cardiac tamponade | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Appropriate descriptive statistics will be provided. |
| Feasibility outcome (study-level): mean enrollment rate of the study | Start of enrollment (date of first patient) to end of enrollment (date of last patient). | Determine whether the mean enrolment rate of the trial (total number of patients recruited / total recruitment period in weeks) is 2 patients per week or more. |
| Proportion of patients requiring pericardiocentesis | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Appropriate descriptive statistics will be provided. |
| Duration of intensive care unit stay | Number of hours in ICU are being collected at the Post-Operative Visit. Hour collection will start upon arrival at ICU post surgery and stop at ICU exit, up to 10 days maximum. | Appropriate descriptive statistics will be provided. |
| Proportion of patients experiencing the composite outcome of death, non-fatal myocardial infarction, or stroke | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Appropriate descriptive statistics will be provided. |
| Proportion of patients requiring a red blood cell transfusion | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Appropriate descriptive statistics will be provided. |
| Feasibility outcome (study-level): crossover rate of the study | Start of enrollment (date of first patient) to end of enrollment (date of last patient). | Determine whether the percentage of crossovers between groups (total number of patients with crossover / total number of patients recruited \* 100) is less than 5%. |
| Feasibility outcome (study-level): percentage of data completion of the study | Start of enrollment (date of first patient) to end of enrollment (date of last patient). | Determine whether the percentage of data completion (total number of patients with complete outcome data / total number of patients enrolled \* 100) is more than 95%. |
Countries
Canada
Contacts
Primary ContactAustin Browne
Backup ContactPatricia Power
Outcome results
None listed