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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (2)

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

Критерии участия

Критерии включения

• ≥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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Hamilton Health Sciences - General Hospital — Hamilton

Публикации

• 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

Идентификаторы

NCT: NCT06622564 · DEPOSITION-2_2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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