The Effects of Intraoperative Tranexamic Acid on Perioperative Bleeding In Craniotomies

NCT06229483 | Recruiting Phase 3 DMC

• 1 other identifier: TXA-2024-01
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Brain Tumor; Bleeding

Outcome Measures

Primary Outcomes (2)

• 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

• Reoperation or disability or death due to intracranial hemorrhage within 30 days

  30 days

Secondary Outcomes (11)

• What is the difference in Hemoglobin level postoperatively as compared to baseline?

  24 hrs

• Number of subjects requiring transfusion of blood products

  30 days

• Volume of transfused packed red blood cell (PRBC) and fresh frozen plasma (FFP)

  30 days

• What is the difference in Intraoperative hemodynamics between subjects?

  Surgery

• Length of operation

  Surgery

Study Arms (2)

Tranexamic Acid

EXPERIMENTAL

Participants will be randomized in a 1:1 ratio to receive tranexamic acid 20 mg/kg IV bolus or identical volume of placebo 0.9 % NaCl within 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. Treatment is blinded.

Drug: TRANEXAMIC ACID 1 G in 10 mL INTRAVENOUS INJECTION, SOLUTION

Matching Placebo

PLACEBO COMPARATOR

Participants will be randomized in a 1:1 ratio to receive tranexamic acid 20 mg/kg IV bolus or identical volume of placebo 0.9 % NaCl within 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. Treatment is blinded.

Other: Placebo

Interventions

Placebo OTHER

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.

Also known as: Normal saline (0.9% sodium chloride)

Matching Placebo

TRANEXAMIC ACID 1 G in 10 mL INTRAVENOUS INJECTION, SOLUTION DRUG

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.

Also known as: TXA

Tranexamic Acid

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stephen Lownie: lead
• Dalhousie University: collaborator

Study Sites (1)

Nova Scotia Health Authority- Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H3A7, Canada

RECRUITING

Related Publications (9)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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.

  PMID: 20554319 RESULT

• 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.

  PMID: 38052364 RESULT

MeSH Terms

Conditions

Brain Neoplasms; Hemorrhage

Interventions

Tranexamic Acid; Injections, Intravenous; Solutions; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Injections; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Stephen Lownie, MD

  Nova Scotia Health Authority- Queen Elizabeth II HSC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Lownie, MD

CONTACT

902-473-6449; stephen.lownie@nshealth.ca

Lisa Julien, RN BScN

CONTACT

902-473-3877; lisa.julien@nshealth.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a blinded study. The participant, surgeon and research team will not know the treatment allocation. Only the pharmacy preparing the medication will be unblinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 29, 2024
• Study Start: April 3, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

CA (1)