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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether tranexamic acid (TXA) can reduce blood loss during brain tumor surgery. Researchers aim to determine if TXA can also decrease the likelihood of needing additional surgery or experiencing serious complications like disability or death from bleeding. Participants will receive either TXA or a placebo (a substance with no active drug) during their surgery, and the results will be compared. Suitable candidates for this trial are those scheduled for brain tumor surgery (craniotomy for tumor resection) who have no history of blood clots or clotting disorders. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that tranexamic acid is likely to be safe for humans?

Research has shown that tranexamic acid (TXA) is generally safe for use in brain tumor surgeries. Studies have found that TXA can reduce blood loss during these operations. Importantly, it does not appear to increase the risk of blood clots or seizures. For instance, one study found that TXA reduced blood loss by about 293 milliliters on average, a significant amount. Another study supported this finding, showing a similar reduction in blood loss. Overall, these results suggest that TXA is safe for use in brain surgery, with no major side effects reported in these studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tranexamic Acid is unique because it specifically targets the reduction of blood loss during brain tumor surgery, which is a significant concern with current surgical treatments. Unlike traditional methods that may rely on blood transfusions or other blood-clotting agents after the fact, Tranexamic Acid works preemptively by stabilizing clots through the inhibition of fibrinolysis, the process that breaks down clots. Researchers are excited about Tranexamic Acid because it has the potential to minimize intraoperative bleeding, leading to safer surgical outcomes and potentially quicker recovery times for patients.

What evidence suggests that tranexamic acid could be effective for reducing blood loss during brain tumor surgery?

Research has shown that tranexamic acid (TXA), which participants in this trial may receive, can help reduce blood loss during brain tumor surgeries. One study found that TXA significantly decreased blood loss without causing issues like blood clots or seizures. Another study demonstrated that TXA reduced blood loss by about 293 mL on average, a significant amount. This treatment might also lower the need for blood transfusions and shorten surgery time. Overall, TXA appears promising in making brain tumor surgeries safer by reducing bleeding. ^{2 3 4 6 7}

Who Is on the Research Team?

Stephen Lownie, MD

Principal Investigator

Nova Scotia Health Authority- Queen Elizabeth II HSC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40763535/

Neuro-oncologic applications of tranexamic acid In brain tumor surgery, TXA appears to successfully reduce blood loss without predisposing patients to VTE or seizure (p < 0.001).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586825005144

Neuro-oncologic applications of tranexamic acid In brain tumor surgery, TXA appears to successfully reduce blood loss without predisposing patients to VTE or seizure (p < 0.001).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06229483

The Effects of Intraoperative Tranexamic Acid on ... 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 ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1464671/full

Intraoperative tranexamic acid administration in cranial ... This meta-analysis suggests that a single intraoperative dose of TXA reduces blood loss, allogeneic blood transfusions and shortens surgery time.

5. surgicalneurologyint.com surgicalneurologyint.com/surgicalint-articles/tranexamic-acid-to-reduce-operative-blood-loss-in-brain-tumor-surgery-a-meta-analysis/

Tranexamic acid to reduce operative blood loss in brain ... TXA resulted in less blood loss with pooled mean difference of −292.80 (95% CI, −431.63, −153.96, P<0.05). The need of transfusion was not ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8326094/

Tranexamic acid to reduce operative blood loss in brain tumor ... All three studies showed that TXA reduced the volume of blood loss with pooled mean difference of −292.80 (95% CI, −431.63, −153.96, P<0.05).

7. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0308070

Efficacy and safety of tranexamic acid on blood loss and ... This systematic review and meta-analysis suggests that the administration of TXA could reduce blood loss in patients undergoing intracerebral meningioma ...