Tranexamic Acid for Spine Surgery Patients

Overseen By Matthew Colman, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rush University Medical Center

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Breastfeeding, Thromboembolic disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 3 days

604 Participants Needed

Trial Summary

What is the purpose of this trial?

As tranexamic acid (TXA) becomes more prevalent, all patients are receiving the same dose and method of delivery regardless of their pre-operative risk of transfusion. Therefore, the aim of the study is to determine whether or not repeated dosing of oral or different method of delivery like intravenous (IV) TXA reduces the postoperative reduction in hemoglobin, hematocrit, number of transfusions, and postoperative blood loss following open spine surgery. The regimen that utilizes multiple doses of oral TXA will significantly minimize post-operative blood loss and transfusion requirements compared to the use of a single dose regimen. Furthermore, oral TXA will be as efficacious as intravenous delivery of TXA.

Will I have to stop taking my current medications?

If you are taking anticoagulant therapy, you must stop it at least five days before surgery to participate in this trial.

What data supports the effectiveness of the drug Tranexamic Acid for spine surgery patients?

Research shows that Tranexamic Acid (TXA) is effective in reducing blood loss during spine surgeries, such as those for thoracolumbar burst fractures and adolescent idiopathic scoliosis. It is widely used as an antifibrinolytic agent (a drug that prevents the breakdown of blood clots) in these procedures. ^{1 2 3 4 5}

Is tranexamic acid generally safe for humans?

Tranexamic acid (TXA) is generally considered safe for use in humans, but there is a rare risk of serious side effects if it is accidentally injected into the spinal canal, which can lead to heart and nerve problems. ^{6 7 8 9 10}

How is the drug Tranexamic Acid unique for spine surgery patients?

Tranexamic Acid (TXA) is unique for spine surgery patients because it is an antifibrinolytic agent that helps reduce blood loss during surgery, which is a common issue in these procedures. Unlike other treatments, TXA is specifically used to minimize the need for blood transfusions by preventing the breakdown of blood clots, although the optimal dosing for complex surgeries is still being studied. ^{2 3 11 12 13}

Research Team

Bryce Basques, MD

Principal Investigator

Rush University Medical Center

Eligibility Criteria

This trial is for adults over 18 scheduled for open posterior thoracolumbar spinal fusion surgery. It's not suitable for those allergic to TXA, refusing blood products, with recent heart attacks, severe lung or liver disease, color vision issues, recent anticoagulant use, kidney impairment, pregnant or breastfeeding women, and those with a history of clotting disorders.

Inclusion Criteria

I am scheduled for a specific back surgery involving the spine.

I am older than 18 years old.

Exclusion Criteria

You are currently breastfeeding.

You are pregnant.

I have kidney problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive either placebo, IV TXA, pre-operative oral TXA, or full oral TXA regimen during and after spine surgery

3 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of transfusion rates and postoperative blood loss

3-4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Tranexamic Acid
• Vitamin C 250 MG Oral Tablet

Trial Overview The study tests if multiple doses of oral Tranexamic Acid (TXA) can reduce post-surgery blood loss and transfusion needs compared to a single dose regimen. It also compares the effectiveness of oral TXA against intravenous delivery in patients undergoing spine surgery.

Participant Groups

Group I: Group 4 Full Oral TXA Experimental Treatment 1 Intervention

Group II: Group 3 Pre-Oral TXA Experimental Treatment 2 Interventions

Group III: Group 2 IV TXA Experimental Treatment 2 Interventions

Group IV: Group 1 PLACEBO Placebo Group 1 Intervention

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?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Findings from Research

Tranexamic acid (TXA) significantly reduces postoperative blood loss and the need for blood transfusions in lumbar surgery, based on a meta-analysis of 49 studies involving 4,822 patients.

TXA improves hemoglobin and hematocrit levels post-surgery without increasing the risk of deep venous thrombosis (DVT), although it does lower D-dimer levels, indicating its effectiveness in promoting hemostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of tranexamic acid in lumbar surgery: A meta-analysis of randomized-controlled trials. Xiao, K., Zhuo, X., Peng, X., et al.[2022]

A study of 36 adult patients undergoing complex spine surgeries showed that high-dose tranexamic acid (TXA) significantly reduced intraoperative blood loss, with an average of 587.1 mL, indicating its efficacy as an antifibrinolytic agent.

No thromboembolic or significant complications were reported, suggesting that high-dose TXA may be safe for use in this surgical context, although further research is needed to confirm its safety and optimal dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of High-Dose Tranexamic Acid in Spine Surgery: A Retrospective Single-Institution Series. Brown, NJ., Pennington, Z., Himstead, AS., et al.[2023]

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]

In a study of 223 patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis, high-dose tranexamic acid (TXA) significantly reduced normalized blood loss by 36% and total estimated blood loss by 37.5% compared to low-dose TXA.

Patients receiving high-dose TXA also experienced a 48% reduction in the need for red blood cell transfusions, with only 19% requiring a transfusion compared to 67% in the low-dose group, highlighting the efficacy of high-dose TXA in managing blood loss during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High- versus low-dose tranexamic acid as part of a Patient Blood Management strategy for reducing blood loss in patients undergoing surgery for adolescent idiopathic scoliosis. Tumber, S., Bacon, A., Stondell, C., et al.[2023]

In a study of 112 adult patients undergoing multilevel posterior spinal fusion surgery, the use of tranexamic acid (TXA) significantly reduced intra- and postoperative blood loss and the need for blood transfusions.

The combined systemic and local application of TXA was found to be a safe and effective strategy for conserving blood during major spinal surgeries, indicating its potential as a standard practice in such procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficiency of Simultaneous Systemic and Topical Use of Tranexamic Acid in Spinal Fusion Surgery. Erdogan, U., Sari, S., Akbas, A.[2022]

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]

Paclitaxel demonstrates significant antiplatelet activity by inhibiting collagen-induced platelet aggregation, with an IC(50) of 59.7, suggesting it may effectively block collagen-mediated signaling pathways.

The drug also interferes with thromboxane A2 (TXA2) synthesis and cytosolic calcium mobilization, indicating a potential mechanism for its cardiovascular benefits beyond its anticancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effects of paclitaxel on platelet aggregation through the inhibition of thromboxane A2 synthase. Lee, JJ., Yu, JY., Lee, JH., et al.[2015]

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]

TXA(2) generation in platelets can occur through different signaling pathways, specifically through αIIbβ3 integrin for ADP and independently via G(12/13) pathways for protease-activated receptors (PARs).

The study identified that while FAK activation is involved in TXA(2) generation, it occurs differently depending on the signaling pathway, indicating a complex interaction between integrin and G(12/13) signaling in platelet function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

G(12/13) signaling pathways substitute for integrin αIIbβ3-signaling for thromboxane generation in platelets. Bhavaraju, K., Lakhani, PR., Dorsam, RT., et al.[2021]

The stable analog of thromboxane A(2), carbocyclic TXA(2) (CTXA(2)), can effectively induce the formation of osteoclast-like cells in murine bone marrow cultures through a RANKL-dependent pathway, highlighting its potential role in bone metabolism.

In contrast, the unstable TXA(2) released from platelets does not contribute to osteoclast formation, as evidenced by the lack of effect from TXA(2) receptor antagonists and the failure of common anti-inflammatory drugs to inhibit osteoclastogenesis induced by platelet-released supernatants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The stable analog carbocyclic TXA2 but not platelet-released TXA2 induces osteoclast-like cell formation. Gruber, R., Schöfnagl, M., Karreth, F., et al.[2019]

Intravenous tranexamic acid (TXA) significantly reduces intraoperative blood loss and total blood loss in patients undergoing complex multilevel spinal surgery, based on a meta-analysis of 7 studies involving 441 patients.

While different dosing regimens of TXA were analyzed, no significant differences in intraoperative blood loss were found among the regimens, although the combination of 15 mg/kg + 1 mg/kg/h showed the most substantial reduction in total blood loss compared to placebo and other doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid dosing strategies and blood loss reduction in multilevel spine surgery: A systematic review and network meta-analysis: Tranexamic acid for multilevel spine surgery. Rahmani, R., Singleton, A., Fulton, Z., et al.[2022]

In a study of 38 patients undergoing short segment pedicle screw fixation for thoracolumbar fractures, the use of tranexamic acid (TXA) significantly reduced intraoperative bleeding compared to a control group.

Patients receiving TXA also experienced less postoperative drainage and did not require any blood transfusions, highlighting its efficacy in minimizing blood loss during spinal surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Tranexamic Acid Reduce Perioperative Bleeding in Short Segment Pedicle Screw Fixation in Thoracolumbar Spine Fractures? Pradhan, RL., Pandey, BK.[2017]

A 20-year-old man experienced anaphylactic shock during spinal surgery due to tranexamic acid (TXA), highlighting a serious safety concern with this increasingly used medication.

This case adds to the growing literature, now totaling five reported instances of anaphylaxis related to TXA in patients with no prior exposure, indicating that even commonly used drugs can pose unexpected risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylactic Reaction to Tranexamic Acid During Posterior Spinal Fusion: A Case Report. Plaster, S., Holy, F., Antony, AK.[2023]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

The efficacy and safety of tranexamic acid in lumbar surgery: A meta-analysis of randomized-controlled trials. [2022]

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

Safety and Efficacy of High-Dose Tranexamic Acid in Spine Surgery: A Retrospective Single-Institution Series. [2023]

3. 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]

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

High- versus low-dose tranexamic acid as part of a Patient Blood Management strategy for reducing blood loss in patients undergoing surgery for adolescent idiopathic scoliosis. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

The Efficiency of Simultaneous Systemic and Topical Use of Tranexamic Acid in Spinal Fusion Surgery. [2022]

6. 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]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

The protective effects of paclitaxel on platelet aggregation through the inhibition of thromboxane A2 synthase. [2015]

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

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

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

G(12/13) signaling pathways substitute for integrin αIIbβ3-signaling for thromboxane generation in platelets. [2021]

10. Scotland pubmed.ncbi.nlm.nih.gov

The stable analog carbocyclic TXA2 but not platelet-released TXA2 induces osteoclast-like cell formation. [2019]

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

Tranexamic acid dosing strategies and blood loss reduction in multilevel spine surgery: A systematic review and network meta-analysis: Tranexamic acid for multilevel spine surgery. [2022]

12. Nepal pubmed.ncbi.nlm.nih.gov

Does Tranexamic Acid Reduce Perioperative Bleeding in Short Segment Pedicle Screw Fixation in Thoracolumbar Spine Fractures? [2017]

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

Anaphylactic Reaction to Tranexamic Acid During Posterior Spinal Fusion: A Case Report. [2023]