The Effects of Intraoperative Tranexamic Acid on Perioperative Bleeding In Craniotomies

Brain Tumor Clinical Trial

Official title:

The Effects of Intraoperative Tranexamic Acid on Perioperative Bleeding In Craniotomies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06229483
• Other study ID #: TXA-2024-01
• Status: Recruiting
• Phase: Phase 3
• Start date: April 3, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: April 2024
• Source: Nova Scotia Health Authority
• Contact: Stephen Lownie, MD
• Phone: 902-473-6449
• Email: stephen.lownie[@]nshealth.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bleeding
• Brain Tumor
• Hemorrhage

Intervention

Drug:
• 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.

Other:
• 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.

Locations

Country	Name	City	State
Canada	Nova Scotia Health Authority- Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia

Sponsors (2)

Lead Sponsor	Collaborator
Stephen Lownie	Dalhousie University

Country where clinical trial is conducted

Canada, 

References & Publications (9)

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 Application — View 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.0000 — View 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, Olaom — View 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.PEDS2143 — View 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 — View 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. — View Citation

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. — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated intraoperative blood loss	a. EBL (ml/kg) = ERCV lost (ml)/[weight (kg) x hematocrit preop/100] i. ERCV = EBV x hematocrit/100 ii. ERCV lost = ERCV preop + ERCV transfused - ERCV postop iii. ERCV transfused = PRBC transfused (ml) x hematocrit transfused PRBC/100 iv. EBV = 75 ml/kg x weight (kg) b. abbreviations used: EBL, estimated blood loss; ERCV, estimated red cell volume; EBV, estimated blood volume; PRBC, packed red blood cells	Surgery
Primary	Reoperation or disability or death due to intracranial hemorrhage within 30 days		30 days
Secondary	What is the difference in Hemoglobin level postoperatively as compared to baseline?		24 hrs
Secondary	Number of subjects requiring transfusion of blood products		30 days
Secondary	Volume of transfused packed red blood cell (PRBC) and fresh frozen plasma (FFP)		30 days
Secondary	What is the difference in Intraoperative hemodynamics between subjects?		Surgery
Secondary	Length of operation		Surgery
Secondary	Length of intensive care unit (ICU)/hospital stay		30 days
Secondary	Medication related risks, including seizure, thromboembolic event		30 days
Secondary	What is the difference in Platelet level postoperatively as compared to baseline?		24 hrs
Secondary	What is the difference in Fibrinogen level postoperatively as compared to baseline?		24 hrs
Secondary	What is the difference in INR/PTT value level postoperatively as compared to baseline?		24 hrs
Secondary	What is the difference in Hematocrit level postoperatively as compared to baseline?		24 hrs