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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| After CPB Tranexamic Acid/Placebo | Active Comparator | In the intervention group, patients will receive intravenous administration (10-100 mL of saline placebo) at the induction of anesthesia as a bolus and/or continuous infusion. In addition, patients will receive intravenous administration (5 g of TxA) after heparin reversal (i.e., after CPB). |
|
| Before CPB Tranexamic Acid/Placebo | Active Comparator | In the control group, patients will receive an intravenous administration (1-10 g of TxA) at the induction of anesthesia as a bolus and/or continuous infusion (i.e., before CPB). In addition, patients will receive an intravenous administration (50 mL of saline placebo) after heparin reversal. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Before CPB Tranexamic Acid | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Measure the level of plasma TxA at 5 time points | 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. | From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. |
| Measure | Description | Time Frame |
|---|---|---|
| Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points | 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. | From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility outcome (study-level): mean enrollment rate of the study | 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. | Start of enrollment (date of first patient) to end of enrollment (date of last patient). |
Inclusion Criteria:
Exclusion Criteria:
Allergy to tranexamic acid
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
Estimated glomerular filtration rate <30 mL/min (CKD-EPI equation) or on dialysis
Pre-operative hemoglobin >170 g/L
Expected circulatory arrest
Pregnancy or breast feeding
Previous enrollment in DEPOSITION trial
Refusal of blood products (e.g., Jehovah's Witnesses)
Isolated Pericardiectomy
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Austin Browne | Contact | 905-527-4322 | 40582 | austin.browne@phri.ca |
| Patricia Power | Contact | 905-527-4322 | 44495 | powerpat@hhsc.ca |
| Name | Affiliation | Role |
|---|---|---|
| Andre Lamy, MD | Hamilton General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hamilton Health Sciences - General Hospital | Hamilton | Ontario | L8L 2X2 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30908754 | Background | Habbab LM, Hussain S, Power P, Bashir S, Gao P, Semelhago L, VanHelder T, Parry D, Chu V, Lamy A. Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study. J Card Surg. 2019 May;34(5):305-311. doi: 10.1111/jocs.14027. Epub 2019 Mar 25. | |
| 38587333 |
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After CPB Tranexamic Acid + Before CPB Placebo versus Before CPB Tranexamic Acid + After CPB Placebo
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|
| After CPB Tranexamic Acid | Drug | Tranexamic acid 5 g (50 mL) administered after heparin reversal (i.e., after CPB). |
|
|
| Before CPB Placebo | Drug | Placebo (10 to 100 mL saline) administered intravenously at the induction of anesthesia as a bolus and/or continuous infusion. |
|
|
| After CPB Placebo | Drug | Placebo (50 mL saline) administered after heparin reversal. |
|
|
| Measure the plasmin generation (i.e., fibrinolytic activity) at 5 time points | 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. | From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning. |
| Feasibility outcome (study-level): crossover rate of the study |
Determine whether the percentage of crossovers between groups (total number of patients with crossover / total number of patients recruited * 100) is less than 5%. |
| Start of enrollment (date of first patient) to end of enrollment (date of last patient). |
| Feasibility outcome (study-level): percentage of data completion of the study | 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%. | Start of enrollment (date of first patient) to end of enrollment (date of last patient). |
| Proportion of patients experiencing an in-hospital seizure | Appropriate descriptive statistics will be provided. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) |
| Proportion of patients requiring any blood product transfusion | Appropriate descriptive statistics will be provided. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) |
| Proportion of patients requiring re-operation for bleeding or cardiac tamponade | Appropriate descriptive statistics will be provided. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) |
| Proportion of patients requiring a red blood cell transfusion | Appropriate descriptive statistics will be provided. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) |
| Proportion of patients requiring pericardiocentesis | Appropriate descriptive statistics will be provided. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) |
| Duration of intensive care unit stay | Appropriate descriptive statistics will be provided. | 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. |
| Proportion of patients experiencing the composite outcome of death, non-fatal myocardial infarction, or stroke | Appropriate descriptive statistics will be provided. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) |
| Lamy A, Sirota DA, Jacques F, Poostizadeh A, Noiseux N, Efremov S, Demers P, Akselrod B, Wang CY, Arora RC, Branny P, McGuinness SP, Brown CD, Jeanmart H, Zhao Q, Zhang H, Belley-Cote EP, Whitlock RP, Browne A, Copland I, Vincent J, Khatun R, Balasubramanian K, Bangdiwala SI, McGillion MH, Fox-Robichaud AE, Spence J, Yusuf S, Devereaux PJ; DEPOSITION Study Group. Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial. Circulation. 2024 Oct 22;150(17):1315-1323. doi: 10.1161/CIRCULATIONAHA.124.069606. Epub 2024 Apr 8. |
| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| D016063 | Blood Loss, Surgical |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007431 | Intraoperative Complications |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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