Tranexamic Acid for Breast Reconstruction

Overseen By Rachel Park, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Virginia

Disqualifiers: Allergy to TXA, Anemia, Pregnancy, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 0-1 week

100 Participants Needed

Trial Summary

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 tranexamic acid generally safe for humans?

Research shows that tranexamic acid is generally safe for humans, with no side effects observed in patients with bleeding disorders after dental procedures, and no toxic effects on the liver, kidney, or heart. ^{1 2 3 4 5}

How is the drug Tranexamic Acid unique for breast reconstruction?

Tranexamic Acid is unique for breast reconstruction because it helps reduce bleeding by preventing the breakdown of blood clots, which is different from other treatments that may focus on different mechanisms or conditions. It is commonly used in surgeries to minimize blood loss, making it particularly useful in procedures like breast reconstruction where managing bleeding is crucial. ^{6 7 8 9 10}

What is the purpose of this trial?

Tranexamic acid (TXA) is a synthetic, competitive lysine receptor inhibitor on plasminogen. It ultimately stabilizes the fibrin matrix, therefore used as a hemostatic agent for various indications. While there has been indications for orthopedic and trauma surgery, there is no clear data for its role in patients who are undergoing free tissue transfer. Studies have shown that patients undergoing free tissue transfer can have transfusion rates ranging from 7.2% to 34.9%, which data also showing association between transfusion requirement and higher free flap failure rate. There has been a few retrospective studies that evaluated the effect of TXA in free tissue transfer and the results showed no increased risk of microanastomosis failure but some showing decreased blood loss. This study aims to further analyze the role of TXA in patients undergoing breast free flap reconstruction with randomized, prospective trial. Control group will not receive TXA while experimental group will receive TXA. Both groups will receive standard of care breast free flap surgery as well as post-op care, which is streamlined with Early Recovery After Surgery (ERAS) protocol. Their pre and post-op hemoglobin will be compared, as well as rates of transfusion, surgical outcome and surgical complications including hematoma, flap failure, and any other medical complications such as Deep Vein Thrombosis (DVT)/ Pulmonary Embolism (PE).

Research Team

John Stranix, MD

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for patients undergoing breast reconstruction with free flap surgery after mastectomy due to breast cancer. Participants must not have a history of clotting or bleeding disorders, and should not be currently receiving anticoagulant therapy. They also need to be fit for the surgical procedure as per standard medical evaluation.

Inclusion Criteria

I am a woman over 18 planning to have breast reconstruction with abdomen tissue at UVA Medical Center.

Exclusion Criteria

I am under 18 years old.

Subjects who are pregnant

Allergy to TXA

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo breast free flap reconstruction surgery with or without TXA administration

0-1 week

1 visit (in-person)

Post-operative Care

Participants receive post-operative care following the ERAS protocol, including monitoring of hemoglobin levels and transfusion rates

0-4 days

Daily monitoring during hospital stay

Follow-up

Participants are monitored for surgical complications and overall recovery, including thromboembolic events and flap failure

30 days

1-2 visits (in-person)

Treatment Details

Interventions

• Tranexamic acid

Trial Overview The study is testing whether Tranexamic acid (TXA), a drug that helps reduce bleeding, can benefit patients during breast reconstruction surgery by comparing it with a placebo. The goal is to see if TXA reduces blood loss, the need for transfusions, and improves surgical outcomes without increasing risks like clot formation.

Participant Groups

Group I: TXA group Experimental Treatment 1 Intervention

Women undergoing immediate or delayed free flap breast reconstruction and receiving IV TXA

Group II: Placebo group Placebo Group 1 Intervention

Women undergoing immediate or delayed free flap breast reconstruction and receiving same volume of IV saline

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

Approved in United States as Lysteda for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma

Approved in European Union as Cyklokapron for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma
• Postpartum hemorrhage

Approved in Japan as Nicolda for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma
• Postpartum hemorrhage

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Findings from Research

Intraoperative injection of tranexamic acid (TXA) during total knee arthroplasty (TKA) significantly reduced postoperative blood loss and the need for blood transfusions, as shown in a study of 100 patients.

The TXA group experienced lower drainage volumes and milder ecchymosis compared to the control group, indicating that TXA is both effective and safe for minimizing hemorrhage during TKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety evaluation of intra-articular injection of tranexamic acid in total knee arthroplasty operation with temporarily drainage close. Wang, G., Wang, D., Wang, B., et al.[2020]

In a double-blind trial involving patients with hemophilia and Christmas disease, tranexamic acid (1 g three times a day for five days) significantly reduced blood loss and the need for blood transfusions after dental extractions.

The study found no side effects or toxic effects on the liver, kidney, or heart, indicating that tranexamic acid is a safe option for managing bleeding in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. Forbes, CD., Barr, RD., Reid, G., et al.[2019]

In a study of 88 patients undergoing total knee arthroplasty, the use of tranexamic acid significantly reduced postoperative blood loss and increased postoperative hemoglobin levels compared to the control group.

The use of tranexamic acid did not increase the risk of deep venous thrombosis (DVT), indicating it is a safe option for managing blood loss during TKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of tranexamic acid in total knee arthroplasty]. Chen, X., Xie, S., Wang, K.[2018]

In a study of 74 breast reduction patients who received intravenous tranexamic acid (TXA) during surgery, there was a significant reduction in postoperative bleeding complications, with only 1.4% experiencing bleeding compared to 16.2% in the control group.

The use of TXA was found to be safe, as there were no significant differences in other complications such as seroma, wound healing issues, or infections, indicating that TXA effectively minimizes hematoma rates without increasing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Usage of Intravenous Tranexamic Acid in Reduction Mammaplasty Safely Reduces Hematoma Rates. Om, A., Marxen, T., Kebede, S., et al.[2023]

In a study of 60 patients undergoing bilateral total knee arthroplasty, intravenous tranexamic acid (TXA) significantly reduced total blood loss and the need for blood transfusions compared to the control group, indicating its efficacy in managing perioperative blood loss.

The use of TXA did not increase the risk of deep vein thrombosis or other thromboembolic events, suggesting it is a safe option for patients undergoing knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A PROSPECTIVE RANDOMIZED SELF-CONTROLLED STUDY ON EFFECT OF TRANEXAMIC ACID IN REDUCING BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY]. Huang, Z., Zhang, W., Li, W., et al.[2018]

Xai-K, a chemically modified non-enzymatic form of Factor Xa, demonstrated significant thrombolytic activity in mice without activating systemic fibrinolysis markers, indicating a safer profile compared to traditional thrombolytic agents like recombinant tPA.

In murine models, Xai-K enhanced clot dissolution by approximately 7-fold and allowed for a more than 30-fold reduction in the required dose of the tPA variant Tenecteplase, suggesting it could improve the efficacy and safety of thrombolytic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombolysis by chemically modified coagulation factor Xa. Pryzdial, EL., Meixner, SC., Talbot, K., et al.[2023]

A new class of selective FXIIIa inhibitors, specifically compound 8, effectively reduces fibrin cross-linking and inhibits clot formation in human plasma, demonstrating a 50% reduction at a concentration of 160 µM.

The effectiveness of compound 8 in promoting fibrinolysis is dose-dependent, meaning higher concentrations lead to faster breakdown of clots when treated with tissue plasminogen activator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors. Leung-Toung, R., Tam, TF., Wodzinska, JM., et al.[2014]

Fondaparinux sodium is a novel antithrombotic agent that specifically inhibits factor Xa and requires binding to antithrombin, making it distinct from traditional heparin and low-molecular-weight heparins.

It has been approved for preventing venous thrombosis after orthopedic surgery with a fixed daily dose of 2.5 mg, eliminating the need for monitoring, which enhances its practicality for patient use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-acting synthetic pentasaccharides as antithrombotic agents. Walenga, JM., Jeske, WP., Fareed, J.[2019]

Fondaparinux sodium is a selective factor Xa inhibitor used for preventing blood clots (thromboprophylaxis) in various patient groups, including those undergoing cesarean delivery.

Recent literature suggests careful consideration of the timing and safety of neuraxial anesthesia in patients who have recently used fondaparinux, highlighting the need for updated guidelines in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal anesthesia for cesarean delivery in a patient receiving fondaparinux. Rentz, JB., Hart, SR., Russo, M.[2021]

Fondaparinux sodium is a highly effective and safe anticoagulant for preventing and treating venous thromboembolic events, with established efficacy in various clinical settings since its approval in 2002.

Recent studies have expanded the use of fondaparinux to additional conditions, such as acute coronary syndromes and in patients intolerant to other anticoagulants, leading to updates in clinical guidelines that recommend its use in these scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fondaparinux Sodium: Recent Advances in the Management of Thrombosis. Bauersachs, RM.[2023]

References

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

Efficacy and safety evaluation of intra-articular injection of tranexamic acid in total knee arthroplasty operation with temporarily drainage close. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. [2019]

3. China pubmed.ncbi.nlm.nih.gov

[Effectiveness of tranexamic acid in total knee arthroplasty]. [2018]

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

The Usage of Intravenous Tranexamic Acid in Reduction Mammaplasty Safely Reduces Hematoma Rates. [2023]

5. China pubmed.ncbi.nlm.nih.gov

[A PROSPECTIVE RANDOMIZED SELF-CONTROLLED STUDY ON EFFECT OF TRANEXAMIC ACID IN REDUCING BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY]. [2018]

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

Thrombolysis by chemically modified coagulation factor Xa. [2023]

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

3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors. [2014]

8. England pubmed.ncbi.nlm.nih.gov

Short- and long-acting synthetic pentasaccharides as antithrombotic agents. [2019]

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

Spinal anesthesia for cesarean delivery in a patient receiving fondaparinux. [2021]

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

Fondaparinux Sodium: Recent Advances in the Management of Thrombosis. [2023]