Tranexamic Acid for Bleeding in Nasal Surgery

Overseen By Connie Ma, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Thromboembolism, Stroke, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 2

Duration: Intraoperative

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will be a prospective randomized control trial to evaluate the effects of subcutaneously administered TXA among patients undergoing nasal Mohs reconstruction with local flaps at VUMC.

Will I have to stop taking my current medications?

The trial information does not specify if 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 reducing bleeding in nasal surgery?

Research shows that Tranexamic Acid (TXA) can reduce bleeding during nasal surgeries like rhinoplasty and septoplasty, which helps minimize the need for blood transfusions and improves surgical conditions. ^{1 2 3 4 5}

Is Tranexamic Acid (TXA) generally safe for use in humans?

Tranexamic Acid (TXA) is generally considered safe for use in humans, as it has been used in various conditions like trauma and surgeries with evidence supporting its tolerability. However, rare cases of accidental intrathecal (spinal) injection can lead to serious side effects, highlighting the importance of correct administration. ^{6 7 8 9 10}

How does the drug tranexamic acid differ from other treatments for bleeding in nasal surgery?

Tranexamic acid (TXA) is unique because it is an antifibrinolytic, meaning it helps prevent the breakdown of blood clots, which can reduce bleeding during and after nasal surgeries. It can be administered in various forms, such as orally, intravenously, or topically, offering flexibility in how it is used to manage bleeding compared to other treatments. ^{1 2 3 5 11}

Research Team

Priyesh Patel, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults over 18 who need nasal reconstruction with local flaps after Mohs surgery for skin cancer at Vanderbilt University Medical Center. It's not open to those having other facial or sinus surgeries at the same time.

Inclusion Criteria

Lack of all the below

I am an adult having a specific nose reconstruction surgery after Mohs surgery at Vanderbilt.

I am not having any other facial or sinus surgery at the same time.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous injections of TXA or standard care during nasal Mohs reconstruction surgery

Intraoperative

1 visit (in-person)

Follow-up

Participants are monitored for postoperative outcomes including bleeding, swelling, bruising, and patient satisfaction

1 week

1 visit (in-person)

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview The study compares two treatments during nasal reconstruction: one group receives tranexamic acid (TXA) plus lidocaine and epinephrine, while the control group gets just lidocaine and epinephrine. The aim is to see if TXA reduces bleeding post-surgery.

Participant Groups

Group I: Experimental Experimental Treatment 1 Intervention

The experimental arm will receive local anesthetic (1% lidocaine with 1:100,000 epinephrine) and TXA (1g/10mL) in a 9:1 volume ratio. This will be injected subcutaneously into the surgical site. The surgical team will inject approximately 0.8mL per square centimeter of the surgical site area (defect area and undermined tissue area).

Group II: Control Active Control 1 Intervention

The control arm will receive the current standard of care. Before incision, local anesthetic (1% lidocaine with 1:100,000 epinephrine) will be injected subcutaneously into the surgical site. The surgical team will inject approximately 0.8mL per square centimeter of the surgical site area (defect area and undermined tissue area).

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?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Findings from Research

Tranexamic acid (TXA) significantly reduces perioperative blood loss and improves surgical field quality during nasal surgeries, based on a meta-analysis of 11 randomized controlled trials.

TXA also helps decrease eyelid edema and ecchymosis after surgery, but it does not significantly affect the duration of the surgical procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of tranexamic acid in nasal surgery: A systemic review and meta-analysis of randomized control trial. Ping, WD., Zhao, QM., Sun, HF., et al.[2022]

In a study of 50 patients undergoing rhinoplasty, preoperative administration of 1 g oral tranexamic acid significantly reduced blood loss during surgery, with an average of 144.6 mL in the TXA group compared to 199.6 mL in the placebo group.

The use of tranexamic acid also led to shorter surgery times and higher surgeon satisfaction regarding the quality of the surgical field, indicating its efficacy and safety in reducing perioperative bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Preoperative Oral Tranexamic Acid on Intraoperative Bleeding During Rhinoplasty. Eftekharian, HR., Rajabzadeh, Z.[2018]

In a study of 176 patients undergoing septoplasty, a single intravenous dose of Tranexamic acid (TXA) significantly reduced postoperative nasal bleeding compared to a control group receiving normal saline.

Patients treated with TXA required less nasal packing and experienced fewer complications, demonstrating that TXA is both effective and safe for preventing bleeding after septoplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of single-dose intravenous tranexamic acid on postoperative nasal bleed in septoplasty. Zaman, SU., Zakir, I., Faraz, Q., et al.[2021]

In a randomized placebo-controlled trial involving 80 patients, Tranexamic acid (TXA) did not significantly reduce intraoperative blood loss during rhinoplasty compared to a placebo, with a mean difference of -3.6 mL (P = 0.65).

Surgeon satisfaction regarding the quality of the surgical field was also not significantly improved with TXA, showing a mean difference of 0.18 (P = 0.22), indicating that TXA may not provide the expected benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Effect of Preoperative Tranexamic Acid on Blood Loss and Field Quality During Rhinoplasty: A Randomized Double-Blinded Controlled Trial. Afzali, SL., Panahi, H., Ganji, F., et al.[2022]

The use of tranexamic acid (TXA) combined with lidocaine and adrenaline during septoplasty significantly reduced bleeding volume compared to the control group, with an average of 187.23 mL in the TXA group versus 341.22 mL in the control group (P=0.001).

Surgeon satisfaction was notably higher in the TXA group, scoring an average of 4.1 compared to 3.16 in the control group (P=0.001), indicating that TXA not only improves surgical conditions but also enhances the overall quality of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of local tranexamic acid on septoplastic surgery quality. Hazrati, E., Haki, BK., Masnour-Ghanaei, A., et al.[2021]

Tranexamic acid (TXA) has shown promising efficacy and tolerability in treating melasma, a challenging skin condition, based on evidence from multiple clinical studies.

TXA can be used alone or alongside other treatments, but there is currently no established consensus or guidelines for its use in melasma, highlighting the need for standardized treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Tranexamic Acid for the Treatment of Melasma: Evidence and Experience-Based Consensus Statement from Indian Experts. Godse, K., Sarkar, R., Mysore, V., 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]

A new class of compounds has been developed that effectively combines thromboxane-A2 receptor antagonism and thromboxane synthase inhibition, showing promising dual activity in inhibiting TxB2 production and platelet aggregation.

Two specific compounds from this series demonstrated strong potency with IC50 values as low as 0.02 to 0.44 microM, and one compound (23m) showed long-lasting effects in vivo, indicating potential for effective oral administration in preventing thromboxane-related platelet activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agents combining thromboxane receptor antagonism with thromboxane synthase inhibition: [[[2-(1H-imidazol-1-yl)ethylidene]amino]oxy]alkanoic acids. Cozzi, P., Giordani, A., Menichincheri, M., et al.[2019]

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]

BM 13.177 is a new drug that effectively inhibits platelet aggregation and thrombus formation in animal models, showing protective effects against sudden death and thrombus formation in rabbits, indicating its potential as an anti-thrombotic agent.

The drug appears to work by antagonizing thromboxane A2 (TXA2), a key player in platelet aggregation and smooth muscle contraction, without the side effects commonly associated with traditional anti-inflammatory drugs, leading to plans for clinical trials in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacological profile of the thromboxane A2 antagonist BM 13.177. A new anti-platelet and anti-thrombotic drug. Stegmeier, K., Pill, J., Müller-Beckmann, B., et al.[2019]

In a study of 60 patients undergoing functional endoscopic sinus surgery, the use of tranexamic acid (TXA) significantly reduced bleeding and improved the quality of the surgical field during the first 30 minutes of the procedure.

The intervention group, which received TXA, showed better surgical field quality compared to the control group, particularly in the first two quarters of the surgery, indicating that TXA is an effective method for enhancing surgical conditions in patients with chronic sinusitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of topical tranexamic acid on bleeding and quality of surgical field during functional endoscopic sinus surgery in patients with chronic rhinosinusitis: a triple blind randomized clinical trial. Jahanshahi, J., Hashemian, F., Pazira, S., et al.[2022]

References

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

Role of tranexamic acid in nasal surgery: A systemic review and meta-analysis of randomized control trial. [2022]

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

The Efficacy of Preoperative Oral Tranexamic Acid on Intraoperative Bleeding During Rhinoplasty. [2018]

3. France pubmed.ncbi.nlm.nih.gov

Effect of single-dose intravenous tranexamic acid on postoperative nasal bleed in septoplasty. [2021]

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

Re-Evaluating the Effect of Preoperative Tranexamic Acid on Blood Loss and Field Quality During Rhinoplasty: A Randomized Double-Blinded Controlled Trial. [2022]

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

Evaluation of local tranexamic acid on septoplastic surgery quality. [2021]

6. India pubmed.ncbi.nlm.nih.gov

Oral Tranexamic Acid for the Treatment of Melasma: Evidence and Experience-Based Consensus Statement from Indian Experts. [2023]

7. 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]

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

Agents combining thromboxane receptor antagonism with thromboxane synthase inhibition: [[[2-(1H-imidazol-1-yl)ethylidene]amino]oxy]alkanoic acids. [2019]

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

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

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

The pharmacological profile of the thromboxane A2 antagonist BM 13.177. A new anti-platelet and anti-thrombotic drug. [2019]

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

Effect of topical tranexamic acid on bleeding and quality of surgical field during functional endoscopic sinus surgery in patients with chronic rhinosinusitis: a triple blind randomized clinical trial. [2022]