Clinical trial NCT06229483: The Effects of Intraoperative Tranexamic Acid on Perioperative Bleeding In Craniotomies
Official title: The Effects of Intraoperative Tranexamic Acid on Perioperative Bleeding In Craniotomies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Brain Tumor
Bleeding
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Dalhousie University
First posted: 2024-01-29
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to receive a 20 mg/kg IV bolus of TXA, or identical volume of placebo 0.9 % NaCl will be administered intravenously push by the anesthesiologist approximately 30 minutes prior to the skin incision followed by a 1 mg/kg/hr infusion of TXA, or identical volume of placebo 0.9 % NaCl, for the duration of surgery
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria are the following:

1. Adult male or female, between 18-80 years of age.
2. Patients are scheduled to undergo a craniotomy for tumor resection.
3. 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.

1. Patients with known active or previous history of thromboembolic disease or deep venous thrombosis.
2. Patients with known pre-existing coagulopathy such as hemophilia, Von Willebrand disease, and clotting factor deficiencies.
3. 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.
4. Female subjects who are pregnant or currently breastfeeding.
5. Patients with Class 3 (high-risk) obesity BMI ≥ to 40.
6. Patients undergoing emergency craniotomy or mini craniotomy or craniectomies.
7. Patients who received embolization prior to surgery.

Primary outcomes:
measure: Estimated intraoperative blood loss
timeFrame: Surgery
measure: Reoperation or disability or death due to intracranial hemorrhage within 30 days
timeFrame: 30 days
Secondary outcomes:
measure: What is the difference in Hemoglobin level postoperatively as compared to baseline?
timeFrame: 24 hrs
measure: Number of subjects requiring transfusion of blood products
timeFrame: 30 days
measure: Volume of transfused packed red blood cell (PRBC) and fresh frozen plasma (FFP)
timeFrame: 30 days
measure: What is the difference in Intraoperative hemodynamics between subjects?
timeFrame: Surgery
measure: Length of operation
timeFrame: Surgery
measure: Length of intensive care unit (ICU)/hospital stay
timeFrame: 30 days
measure: Medication related risks, including seizure, thromboembolic event
timeFrame: 30 days
measure: What is the difference in Platelet level postoperatively as compared to baseline?
timeFrame: 24 hrs
measure: What is the difference in Fibrinogen level postoperatively as compared to baseline?
timeFrame: 24 hrs
measure: What is the difference in INR/PTT value level postoperatively as compared to baseline?
timeFrame: 24 hrs
measure: What is the difference in Hematocrit level postoperatively as compared to baseline?
timeFrame: 24 hrs
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: Nova Scotia Health Authority- Queen Elizabeth II Health Sciences Center
state: Nova Scotia
Study officials:
affiliation: Nova Scotia Health Authority- Queen Elizabeth II HSC
name: Stephen Lownie, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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 blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.
citation: Brown NJ, Hartke JN, Pacult M, Burkett KR, Gendreau J, Catapano JS, Lawton MT. Tranexamic Acid Demonstrates Efficacy without Increased Risk for Venous Thromboembolic Events in Cranial Neurosurgery: Systematic Review of the Evidence and Current Applications in Nontraumatic Pathologies. World Neurosurg. 2024 Mar;183:29-40. doi: 10.1016/j.wneu.2023.11.148. Epub 2023 Dec 3.