Tranexamic Acid for Spinal Injury

Recruiting at 5 trial locations

Overseen By Matthew J. Cooney

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Columbia University

Must not be taking: Anticoagulants, NSAIDs, Factor IX

Disqualifiers: Age <18 or >80, Sepsis, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

252 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to evaluate the efficacy of topical tranexamic acid to reduce perioperative blood loss, reduction in postoperative drain output and allogenic transfusion requirements. The proposed study will be a prospective, randomized, double-blind (subject, surgeons, investigators, research coordinators) placebo-controlled study. Patients requiring posterior spinal fusion will be enrolled for this study. Furthermore, patients undergoing elective complex deformity surgery will also be enrolled. Both populations of patients will be randomized into two groups. Group I will receive standard of care operative fixation with topical tranexamic acid intervention (test); Group II will receive standard of care operative fixation with normal saline (placebo) intervention. This study will have a 2-year follow-up and will consist of three periods: screening/enrollment phase up to 21 days from the day of injury to the day of randomization and operative intervention, an inpatient data collection period for 4 days postoperative, and then a follow-up period for 2-years postoperative (visits occurring at 16 weeks, 1 year, and 2 year) time points.

Will I have to stop taking my current medications?

The trial requires that you stop taking anticoagulant medications (like heparin or warfarin) three days before surgery and non-steroidal anti-inflammatory drugs (like aspirin or ibuprofen) seven days before surgery. If you are on these medications, you will need to stop them before participating.

What data supports the effectiveness of the drug Tranexamic Acid (TXA) for spinal injury?

Research suggests that Tranexamic Acid (TXA) can reduce bleeding after physical trauma, which may help in managing spinal cord injuries where bleeding is a concern. ^{1 2 3 4 5}

Is tranexamic acid generally safe for humans?

Tranexamic acid (TXA) is generally used to reduce bleeding in trauma and surgeries, but accidental injection into the spine can be dangerous, causing heart and nerve problems. This highlights the importance of correct administration to ensure safety. ^{4 6 7 8 9}

How does the drug tranexamic acid differ from other treatments for spinal injury?

Tranexamic acid is unique because it is an antifibrinolytic drug that helps reduce blood loss during surgery by preventing the breakdown of blood clots. Unlike other treatments, it can be administered topically, which may reduce the risk of severe side effects associated with intravenous administration. ^{10 11 12 13 14}

Research Team

Ronald A Lehman, M.D.

Principal Investigator

Columbia University

Eligibility Criteria

Adults with thoracic or lumbar spine injuries from trauma or needing complex surgery, who can have surgery within 21 days of injury and require long spinal fusions. Excluded are those with low hemoglobin, recent anticoagulant use, severe brain injuries, other trial participation, certain blood disorders, pregnancy/breastfeeding, history of thrombosis or seizures, major organ damage or serious comorbidities.

Inclusion Criteria

My surgery is scheduled within 3 weeks of my injury.

I need surgery for a spine injury in my chest or lower back area.

I am having a spinal fusion surgery involving more than 5 levels.

Exclusion Criteria

I have significant kidney or liver problems.

Ballistic spinal column injury

Allergy to tranexamic acid

Timeline

Screening/Enrollment

Participants are screened for eligibility to participate in the trial

Up to 3 weeks

1 visit (in-person)

Inpatient Data Collection

Participants undergo surgery and data is collected for 4 days postoperatively

4 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 2 weeks, 16 weeks, 1 year, and 2 years

Treatment Details

Interventions

• Placebo
• Tranexamic Acid

Trial Overview The study tests if tranexamic acid reduces blood loss during and after spine trauma surgery compared to a placebo. It's randomized and double-blind meaning neither the patients nor the doctors know who gets the real treatment versus saline solution. The follow-up is for two years with several check-ins.

Participant Groups

Group I: Intervention Active Control 1 Intervention

Subjects will receive tranexamic acid on the surgical wound.

Group II: Placebo control Placebo Group 1 Intervention

Subjects will receive placebo (saline solution) on the surgical wound.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study of 46 patients with acute cervical spinal cord injury, high-dose methylprednisolone sodium succinate (MPSS) was associated with a higher rate of complications (56.5%) compared to placebo (34.8%), although this difference was not statistically significant.

Significantly more pulmonary complications (34.8% vs. 4.34%) and gastrointestinal complications (17.4% vs. 0%) were observed in the MPSS group, particularly in patients over 60 years old, indicating that older patients may require closer monitoring when receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. Matsumoto, T., Tamaki, T., Kawakami, M., et al.[2022]

There is currently insufficient evidence to recommend the use of methylprednisolone for improving clinical outcomes in patients with thoracic and lumbar fractures and spinal cord injury.

The task force emphasized the importance of considering the potential complications associated with methylprednisolone administration before making treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma: Pharmacological Treatment. Arnold, PM., Anderson, PA., Chi, JH., et al.[2019]

In a mouse model of spinal cord injury (SCI), tranexamic acid (TXA) significantly reduced intralesional bleeding and heme levels, which are associated with tissue damage and inflammation.

TXA treatment led to decreased expression of the inflammatory markers TLR4 and TNF in microglial cells, resulting in improved functional recovery after SCI, suggesting its potential as a therapeutic option in the acute phase of spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid reduces heme cytotoxicity via the TLR4/TNF axis and ameliorates functional recovery after spinal cord injury. Yoshizaki, S., Kijima, K., Hara, M., et al.[2023]

In a case of accidental intrathecal injection of tranexamic acid (TXA) during hip surgery, the patient experienced severe neurological and cardiac complications, highlighting the potential dangers of this medication when misadministered.

The treatment involving ventriculolumbar perfusion with saline and inhalational sedation with sevoflurane showed promise in managing TXA-induced neurotoxicity, suggesting a potential approach for similar cases, although complete recovery was not achieved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventriculolumbar perfusion and inhalational anesthesia with sevoflurane in an accidental intrathecal injection of tranexamic acid: unreported treatment options. Godec, S., Gradisek, MJ., Mirkovic, T., et al.[2022]

In a study involving 620 patients (290 treated with dexamethasone and 330 as controls), those receiving dexamethasone showed greater improvement in recovery from acute spinal cord injuries compared to those who did not receive corticosteroids.

While dexamethasone treatment was effective, it was associated with a slight increase in complications like gastrointestinal bleeding and delayed wound healing, highlighting the need for careful monitoring when used shortly after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of dexamethasone in the treatment of acute spinal cord injury. Kiwerski, JE.[2019]

This pilot study aims to assess the safety and feasibility of administering oral glyburide to 10 patients with acute cervical spinal cord injury within 8 hours of injury, building on preclinical evidence that glyburide can reduce secondary injury effects like progressive hemorrhagic necrosis.

Glyburide is considered a promising neuroprotective strategy due to its potential to mitigate secondary injury mechanisms, despite the risk of hypoglycemia, making it an interesting addition to standard care for spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SCING-Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA. Minnema, AJ., Mehta, A., Boling, WW., et al.[2020]

The study demonstrated that the TXA2 receptor antagonist BAY U 3405 effectively blocks TXA2-mediated processes, which are linked to sudden death in a model of AA-induced mortality, indicating its potential as a therapeutic agent.

BAY U 3405 shows a rapid onset and long duration of action, with effective doses ranging from 1 to 3 mg/kg, suggesting it could be beneficial for treating diseases associated with TXA2 dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of BAY U 3405, a new thromboxane antagonist, on arachidonic acid induced thromboembolism. Seuter, F., Perzborn, E., Fiedler, VB.[2013]

In a study involving 30 patients with early cervical myelopathy, Riluzole did not show significant improvements in clinical outcomes or diffusion tensor imaging (DTI) metrics after one month of treatment compared to a placebo group.

Despite the lack of significant changes in clinical scores and DTI indices, the study suggests that further research is necessary to explore the potential role of Riluzole in treating cervical myelopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy: a double-blinded, placebo-controlled randomised controlled trial. Rajasekaran, S., Aiyer, SN., Shetty, AP., et al.[2018]

The study investigated the relationship between TXA2 and PGI2 levels and secondary trauma following spinal cord injury using a rabbit model, providing insights into the biochemical changes that occur after injury.

Intra-arachnoid perfusion of dexamethasone and verapamil was evaluated for its effects on TXA2-PGI2 alterations, suggesting potential therapeutic interventions to mitigate secondary damage after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intra-arachnoid space perfusion on thromboxane A and prostacycline in experimental spinal cord injury. Tu, Y., Du, J., Xia, Z., et al.[2019]

Tranexamic acid (TXA) significantly reduces total and intraoperative blood loss during scoliosis surgery, based on a meta-analysis of 685 patients, indicating its efficacy as a treatment option.

There was no significant difference in the need for blood transfusions between the TXA and placebo groups, suggesting that while TXA helps control blood loss, it does not necessarily reduce transfusion requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tranexamic acid in reducing blood loss in scoliosis surgery: a systematic review and meta-analysis. Yuan, QM., Zhao, ZH., Xu, BS.[2018]

Tranexamic acid (TXA) significantly reduces hidden blood loss, total blood loss, and maximum hemoglobin drop in patients undergoing pedicle screw fixation for thoracolumbar burst fractures, especially with a two-dose regimen.

The use of TXA does not adversely affect liver and renal function, coagulation, or increase the risk of complications, while also lowering post-operative inflammatory markers like interleukin-6 and C-reactive protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of multiple-dose intravenous tranexamic acid in reducing perioperative blood loss in patients with thoracolumbar burst fracture. Wang, F., Nan, L., Feng, X., et al.[2021]

Topical tranexamic acid (TXA) significantly reduced postoperative blood loss in spine surgery patients compared to a placebo, with a large effect size (SMD 2.21) based on a review of 218 patients across six studies.

Patients receiving topical TXA also experienced shorter hospital stays, indicating its potential to improve recovery times in spinal surgery, although more research is needed to determine optimal dosing and pharmacodynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical tranexamic acid in spinal surgery: A systematic review and meta-analysis. Yerneni, K., Burke, JF., Tuchman, A., et al.[2019]

In a study of 51 patients undergoing posterior spinal fusion for adult spinal deformity, the use of epsilon aminocaproic acid (EACA) significantly reduced total blood loss compared to placebo, highlighting its efficacy as an antifibrinolytic agent.

While both EACA and tranexamic acid (TXA) showed trends toward reduced intraoperative blood loss, EACA was more effective in lowering postoperative blood transfusion rates compared to TXA, suggesting it may be the preferred choice for minimizing blood loss in these surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antifibrinolytics reduce blood loss in adult spinal deformity surgery: a prospective, randomized controlled trial. Peters, A., Verma, K., Slobodyanyuk, K., et al.[2022]

Tranexamic acid (TXA) significantly reduces intraoperative blood loss, transfusion rates, and postoperative drainage volume in adolescent spinal corrective surgery, indicating its efficacy in this context.

The administration of TXA is generally safe, with no drug-related adverse events reported at doses ranging from 10-100 mg/kg for loading and 1-10 mg/(kg·h) for maintenance, although further research is needed to optimize these dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Progress on the application of tranexamic acid in adolescent spine corrective surgery]. Zhang, Z., Yang, X., Wang, L., et al.[2022]

References

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

Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. [2022]

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

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma: Pharmacological Treatment. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid reduces heme cytotoxicity via the TLR4/TNF axis and ameliorates functional recovery after spinal cord injury. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Ventriculolumbar perfusion and inhalational anesthesia with sevoflurane in an accidental intrathecal injection of tranexamic acid: unreported treatment options. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Application of dexamethasone in the treatment of acute spinal cord injury. [2019]

6. England pubmed.ncbi.nlm.nih.gov

SCING-Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA. [2020]

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

Effect of BAY U 3405, a new thromboxane antagonist, on arachidonic acid induced thromboembolism. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

Effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy: a double-blinded, placebo-controlled randomised controlled trial. [2018]

9. China pubmed.ncbi.nlm.nih.gov

Effect of intra-arachnoid space perfusion on thromboxane A and prostacycline in experimental spinal cord injury. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tranexamic acid in reducing blood loss in scoliosis surgery: a systematic review and meta-analysis. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy and safety of multiple-dose intravenous tranexamic acid in reducing perioperative blood loss in patients with thoracolumbar burst fracture. [2021]

12. Scotland pubmed.ncbi.nlm.nih.gov

Topical tranexamic acid in spinal surgery: A systematic review and meta-analysis. [2019]

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

Antifibrinolytics reduce blood loss in adult spinal deformity surgery: a prospective, randomized controlled trial. [2022]

14. China pubmed.ncbi.nlm.nih.gov

[Progress on the application of tranexamic acid in adolescent spine corrective surgery]. [2022]