Tranexamic Acid for Brain Tumor Surgery

Overseen By Lisa Julien, RN BScN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stephen Lownie

Disqualifiers: Thromboembolic disease, Coagulopathy, Renal impairment, Pregnancy, Obesity, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: During surgery

102 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Tranexamic Acid for brain tumor surgery?

Research shows that Tranexamic Acid (TXA) can reduce bleeding during surgeries, such as those for brain and spinal tumors, without increasing the risk of complications like blood clots. This suggests it may help control bleeding during brain tumor surgeries as well. ^{1 2 3 4 5}

Is tranexamic acid generally safe for use in surgeries?

Tranexamic acid (TXA) is generally safe for use in surgeries, as it helps reduce bleeding and the need for blood transfusions. However, it can occasionally cause seizures, especially after neurosurgery or cardiac surgery. ^{1 6 7 8 9}

How is the drug Tranexamic Acid unique for brain tumor surgery?

Tranexamic Acid (TXA) is unique for brain tumor surgery because it helps reduce bleeding during the operation, which is crucial for surgeries involving highly vascular tumors. Unlike other treatments, TXA is specifically used to limit blood loss, although its role in elective cranial surgeries is not yet well established. ^{1 3 10 11 12}

Research Team

Stephen Lownie, MD

Principal Investigator

Nova Scotia Health Authority- Queen Elizabeth II HSC

Eligibility Criteria

This trial is for adults aged 18-80 who are scheduled to have brain surgery (craniotomy) to remove a tumor. They must be able to give written consent themselves or through a decision maker.

Inclusion Criteria

Patients/Substitute Decision Maker have given written consent to participate

I am scheduled for a surgery to remove a brain tumor.

Exclusion Criteria

I had a procedure to block blood flow to my tumor before surgery.

I have a history of blood clots or deep vein thrombosis.

My BMI is 40 or higher, indicating high-risk obesity.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tranexamic acid or placebo during surgery to assess its effect on blood loss

During surgery

Follow-up

Participants are monitored for safety and effectiveness after surgery, focusing on bleeding-related complications

4 weeks

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview The study tests if tranexamic acid (TXA), given as an initial dose and then as an infusion during surgery, can reduce blood loss in patients having brain tumor removal surgeries compared to a placebo.

Participant Groups

Group I: Tranexamic Acid Experimental Treatment 1 Intervention

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.

Group II: Matching Placebo Placebo Group 1 Intervention

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.

Tranexamic Acid is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in European Union as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries
• Hereditary angioedema

Approved in Canada as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in Japan as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Who Is Running the Clinical Trial?

Stephen Lownie

Lead Sponsor

Trials

1

Recruited

100+

Dalhousie University

Collaborator

Trials

177

Recruited

402,000+

Findings from Research

In a study of 600 patients undergoing meningioma resection, tranexamic acid (TXA) did not significantly increase the risk of postoperative seizures compared to a placebo, with seizure rates of 4.3% in the TXA group versus 3.7% in the placebo group.

TXA also did not significantly reduce intraoperative bleeding, indicating that while it is safe in this context, it may not provide the expected benefits in terms of blood loss during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tranexamic acid for intracerebral meningioma resections: A randomized, parallel-group, non-inferiority trial. Li, S., Liu, M., Yang, J., et al.[2023]

In a study of 83 patients undergoing spinal tumor surgery, the use of tranexamic acid (TXA) did not significantly reduce overall, intraoperative, or postoperative blood loss, indicating its moderate efficacy in this context.

However, the TXA group experienced a significant reduction in the volume of blood transfusions needed, without any increase in postoperative complications, suggesting that TXA may help minimize the need for transfusions during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood loss and perioperative transfusions related to surgery for spinal tumors. Relevance of tranexamic acid. Damade, C., Tesson, G., Gilard, V., et al.[2020]

In a study involving 91 patients undergoing intracranial meningioma resection, the use of tranexamic acid (TXA) significantly reduced total blood loss during surgery (283 ml vs. 576 ml for placebo; P < 0.001).

Despite the reduction in blood loss, TXA did not significantly decrease the need for blood transfusions, and the rates of thrombotic complications, seizures, and hematoma formation were similar between the TXA and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial. Rebai, L., Mahfoudhi, N., Fitouhi, N., et al.[2022]

In a study of 126 patients undergoing surgery for aggressive bone tumors, those who received tranexamic acid (TXA) ambulated significantly further and participated longer in physical therapy sessions compared to those who did not receive TXA, especially on postoperative Days 1 and 2.

The increased ambulation associated with TXA administration correlated with a shorter hospital stay and a higher likelihood of being discharged home, highlighting its potential benefits in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction. Haase, DR., Mersereau, EJ., Kimbrel, B., et al.[2022]

Intraoperative use of tranexamic acid (TXA) during spinal canal tumor resection significantly reduced intraoperative blood loss and postoperative drainage compared to a control group, indicating its efficacy in managing surgical bleeding.

The study found no increase in thrombotic complications or adverse effects related to coagulation function, suggesting that TXA is a safe option for patients undergoing spinal surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tranexamic acid in spinal canal tumors: a retrospective cohort study. Zhang, HZ., Dong, L., Wang, HM., et al.[2020]

Tranexamic acid (TXA) is effective in reducing blood loss and the need for blood transfusions across various types of surgeries, including orthopedic and cardiac procedures, based on a systematic review of 47 meta-analyses involving numerous outcomes.

TXA is generally safe, showing no increase in death or vascular adverse events, although it may pose a risk for seizures in cardiac surgery, highlighting the need for tailored dosing recommendations for different surgical types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Tranexamic Acid Reduce the Blood Loss in Various Surgeries? An Umbrella Review of State-of-the-Art Meta-Analysis. Hong, P., Liu, R., Rai, S., et al.[2022]

Tranexamic acid (TXA) significantly reduces the rate of hematoma expansion in patients with traumatic brain injury (TBI), which can lead to lower mortality rates and improved neurologic outcomes, based on a systematic review of 5 randomized controlled trials involving 917 patients.

The effectiveness of TXA is enhanced when treatment is administered early, and it does not increase the risk of thrombosis events, indicating it is a safe option for managing hemorrhage in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Weng, S., Wang, W., Wei, Q., et al.[2019]

In a clinical trial involving 356 patients with hematologic malignancies, prophylactic use of tranexamic acid (TXA) did not significantly reduce the incidence of WHO grade ≥2 bleeding compared to a placebo, with bleeding observed in 50.3% of the TXA group and 54.2% of the placebo group.

There were no significant differences in platelet transfusions, days alive without bleeding, or serious adverse events between the TXA and placebo groups, indicating that TXA may not be effective for preventing bleeding in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo-controlled, randomized clinical trial. Gernsheimer, TB., Brown, SP., Triulzi, DJ., et al.[2023]

A meta-analysis of 16 studies involving 45,235 patients found that tranexamic acid (TXA) therapy during adult cardiac surgery significantly increases the risk of seizures, with a 4.1-fold higher incidence compared to controls.

This increased risk of seizures was consistent across various study types, including randomized controlled trials and observational studies, indicating a robust association regardless of the study design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies. Takagi, H., Ando, T., Umemoto, T.[2017]

A systematic review of 4 studies involving 682 patients found that tranexamic acid (TXA) significantly reduced the need for blood transfusions during elective cranial surgeries, indicating its efficacy in minimizing intraoperative blood loss.

Patients receiving TXA experienced a mean total blood loss of 821.9 mL compared to 1099.0 mL in the control group, although there was no significant difference in postoperative hemoglobin levels between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Tranexamic Acid for Elective Resection of Intracranial Neoplasms: A Systematic Review. Brown, NJ., Wilson, B., Ong, V., et al.[2022]

Tranexamic acid (TXA) was successfully used in two infants undergoing surgery for choroid plexus papilloma (CPP), resulting in minimal blood loss of less than 20% of their total circulating blood volume.

This study suggests that TXA may be an effective hemostatic agent during the surgical removal of vascular tumors in infants, warranting further investigation into its use in this sensitive population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tranexamic acid in infants undergoing choroid plexus papilloma surgery: a report of two cases. Phi, JH., Goobie, SM., Hong, KH., et al.[2014]

This study aims to determine the optimal dose of tranexamic acid (TXA) for reducing intraoperative bleeding in patients undergoing neurosurgical resection of meningiomas larger than 5 cm, involving a randomized trial with different dosing groups.

The primary outcome will measure intraoperative blood loss, while secondary outcomes will assess coagulation function and blood product infusion, providing insights into the efficacy and safety of TXA in this specific surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tranexamic acid on intraoperative blood loss in patients undergoing brain meningioma resections: Study protocol for a randomized controlled trial. Yu, H., Liu, M., Zhang, X., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intravenous tranexamic acid for intracerebral meningioma resections: A randomized, parallel-group, non-inferiority trial. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Blood loss and perioperative transfusions related to surgery for spinal tumors. Relevance of tranexamic acid. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tranexamic acid in spinal canal tumors: a retrospective cohort study. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Does Tranexamic Acid Reduce the Blood Loss in Various Surgeries? An Umbrella Review of State-of-the-Art Meta-Analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo-controlled, randomized clinical trial. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Use of Tranexamic Acid for Elective Resection of Intracranial Neoplasms: A Systematic Review. [2022]

11. France pubmed.ncbi.nlm.nih.gov

Use of tranexamic acid in infants undergoing choroid plexus papilloma surgery: a report of two cases. [2014]

12. United States pubmed.ncbi.nlm.nih.gov

The effect of tranexamic acid on intraoperative blood loss in patients undergoing brain meningioma resections: Study protocol for a randomized controlled trial. [2023]