Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid 2 Pilot Trial

Official title

Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION)-2 Pilot Trial

Overview

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

• Drug Before 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).
• Drug After CPB Tranexamic Acid
  Tranexamic acid 5 g (50 mL) administered after heparin reversal (i.e., after CPB).
• Drug Before CPB Placebo
  Placebo (10 to 100 mL saline) administered intravenously at the induction of anesthesia as a bolus and/or continuous infusion.
• Drug After CPB Placebo
  Placebo (50 mL saline) administered after heparin reversal.

Primary outcome measures

• Measure the level of plasma TxA at 5 time points [Time frame: From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.]

Secondary outcome measures (2)

• Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points [Time frame: 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 [Time frame: From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.]

Eligibility criteria

Inclusion criteria

• ≥18 years of age
• 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
• Provide written informed consent

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Hamilton Health Sciences - General Hospital — Hamilton

Publications

• 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. PMID 30908754
• 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 Tranexa PMID 38587333

Identifiers

NCT: NCT06622564 · DEPOSITION-2_2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗