The Effects of Intraoperative Tranexamic Acid on Perioperative Bleeding In Craniotomies

Обзор

The goal of this clinical trial is to test the effect of a drug called tranexamic acid (TXA) on reducing blood loss in participants undergoing surgery to remove brain tumors. The main questions it aims to answer are: 1. Does TXA 20 mg/kg IV bolus of TXA, and 1 mg/kg/hr infusion of TXA reduce the amount of estimated blood loss during surgery? 2. Does TXA 20 mg/kg IV bolus of TXA, and 1 mg/kg/hr infusion of TXA prevent re-operation, disability or death related to bleeding inside the head during and after surgery? Participants are randomized to receive 20 mg/kg IV bolus of TXA or matching placebo within 30 minutes of start of surger, and then 1 mg/kg/hr infusion of TXA or matching from the start of surgery to end of surgery. Treatment allocation is blinded. Investigator will compare the two treatment arms to see whether there are differences in the amount of blood loss during surgery and bleeding-related complications. Investigators will also monitor for any side effects of TXA.

Подробное описание

Excessive blood loss during and after a neurosurgical procedure may increase illness and cause death. The surgeons and their team put in a lot of effort during surgery to and prevent excessive bleeding during and after surgery. One of the medications that may help is tranexamic acid (TXA). TXA is a medication that is widely used in cardiac, orthopedic and trauma surgery to prevent heavy bleeding, the need for blood transfusion and reduce death. During neurosurgery, there is not enough proof whether giving TXA to participants reduces blood loss, and there are no clear guidelines regarding the use of TXA. Investigators are interested in studying the effect of TXA on blood loss in participants undergoing craniotomy to remove a brain tumor. A craniotomy is an operation where a piece of the skull is removed to show part of the brain to remove a brain tumor. One of the risks associated with this procedure is bleeding. Currently, some participants undergoing this type of surgery receive TXA and others do not, as the decision to administer TXA is based on an investigator's preference. Therefore, a study investigating the impact of TXA on bleeding during or following craniotomy, as well as its safety, is needed to better inform practice and potentially improve outcomes of surgery.

Вмешательства

• Препарат TRANEXAMIC ACID 1 G in 10 mL INTRAVENOUS INJECTION, SOLUTION
  Tranexamic acid 20 mg/kg IV bolus within 30 minutes prior to the skin incision followed by a 1 mg/kg/hr infusion of TXA, for the duration of surgery. Treatment is blinded.
• Другое Placebo
  0.9% normal saline 20ml/kg IV bolus within 30 minutes prior to the skin incision followed by a 1 ml/kg/hr infusion of 0.9 % sodium chloride for the duration of surgery. Treatment is blinded.

Первичные конечные точки

• Estimated intraoperative blood loss [Срок оценки: Surgery]
• Reoperation or disability or death due to intracranial hemorrhage within 30 days [Срок оценки: 30 days]

Вторичные конечные точки (11)

• What is the difference in Hemoglobin level postoperatively as compared to baseline? [Срок оценки: 24 hrs]
• Number of subjects requiring transfusion of blood products [Срок оценки: 30 days]
• Volume of transfused packed red blood cell (PRBC) and fresh frozen plasma (FFP) [Срок оценки: 30 days]
• What is the difference in Intraoperative hemodynamics between subjects? [Срок оценки: Surgery]
• Length of operation [Срок оценки: Surgery]
• Length of intensive care unit (ICU)/hospital stay [Срок оценки: 30 days]
• Medication related risks, including seizure, thromboembolic event [Срок оценки: 30 days]
• What is the difference in Platelet level postoperatively as compared to baseline? [Срок оценки: 24 hrs]
• What is the difference in Fibrinogen level postoperatively as compared to baseline? [Срок оценки: 24 hrs]
• What is the difference in INR/PTT value level postoperatively as compared to baseline? [Срок оценки: 24 hrs]
• What is the difference in Hematocrit level postoperatively as compared to baseline? [Срок оценки: 24 hrs]

Критерии участия

Inclusion Criteria are the following:

• Adult male or female, between 18-80 years of age.
• Patients are scheduled to undergo a craniotomy for tumor resection.
• Patients/ Substitute Decision Maker have given written consent to participate.

Exclusion Criteria are the following: Patients who meet any of the following exclusion criteria will not be eligible.

• Patients with known active or previous history of thromboembolic disease or deep venous thrombosis.
• Patients with known pre-existing coagulopathy such as hemophilia, Von Willebrand disease, and clotting factor deficiencies.
• Patients with renal impairment and eGFR <60 ml/min/1.73 m2 as determined by the lab or calculated by using the Cockcroft Gault formula or end stage renal disease currently on dialysis.
• Female subjects who are pregnant or currently breastfeeding.
• Patients with Class 3 (high-risk) obesity BMI ≥ to 40.
• Patients undergoing emergency craniotomy or mini craniotomy or craniectomies.
• Patients who received embolization prior to surgery.

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

Простое слепое

Основная цель

Профилактика

Центры проведения

Канада · 1 центр

• Nova Scotia Health Authority- Queen Elizabeth II Health Sciences Center — Halifax

Публикации

• Rajagopalan V, Chouhan RS, Pandia MP, Lamsal R, Rath GP. Effect of Intraoperative Blood Loss on Perioperative Complications and Neurological Outcome in Adult Patients Undergoing Elective Brain Tumor Surgery. J Neurosci Rural Pract. 2019 Oct;10(4):631-640. doi: 10.1055/s-0039-3399487. Epub 2019 Dec 11. PMID 31831982
• Rolston JD, Han SJ, Lau CY, Berger MS, Parsa AT. Frequency and predictors of complications in neurological surgery: national trends from 2006 to 2011. J Neurosurg. 2014 Mar;120(3):736-45. doi: 10.3171/2013.10.JNS122419. Epub 2013 Nov 22. PMID 24266542
• Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci. 2017 Jul;41:132-138. doi: 10.1016/j.jocn.2017.02.053. Epub 2017 Mar 7. PMID 28283245
• Vel R, Udupi BP, Satya Prakash MV, Adinarayanan S, Mishra S, Babu L. Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients. Saudi J Anaesth. 2015 Jan;9(1):42-8. doi: 10.4103/1658-354X.146304. PMID 25558198
• Eustache G, Nardi N, Rousseau C, Aouaissia S, Aillet S, Delahaye Larralde S, Wodey E, Riffaud L. Importance of tranexamic acid in pediatric monosutural craniosynostosis surgery. J Neurosurg Pediatr. 2021 Dec 24;29(4):412-418. doi: 10.3171/2021.10.PEDS21438. Print 2022 Apr 1. PMID 34952528
• Crantford JC, Wood BC, Claiborne JR, Ririe DG, Couture DE, Thompson JT, David LR. Evaluating the safety and efficacy of tranexamic acid administration in pediatric cranial vault reconstruction. J Craniofac Surg. 2015 Jan;26(1):104-7. doi: 10.1097/SCS.0000000000001271. PMID 25534062
• Wu B, Lu Y, Yu Y, Yue H, Wang J, Chong Y, Cui W. Effect of tranexamic acid on the prognosis of patients with traumatic brain injury undergoing craniotomy: study protocol for a randomised controlled trial. BMJ Open. 2021 Nov 25;11(11):e049839. doi: 10.1136/bmjopen-2021-049839. PMID 34824110
• CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and bloo PMID 20554319

Идентификаторы

NCT: NCT06229483 · TXA-2024-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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