TXA for Gender Affirming Mastectomy

(IVTXA Trial)

Recruiting at 1 trial location

Overseen By Israel O Falade, BS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Coagulopathy, Thromboembolic events, 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: 1

Duration: 1 day

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Gender affirming surgeries (GAS) have been steadily increasing in the US, with the gender affirming mastectomy (GAM) being the most common surgery performed. Complications associated with these surgeries include hematoma and seroma. Prior studies in orthopedics, plastic surgery, and trauma have shown significant reduction of bleeding and ecchymosis with the use of tranexamic acid (TXA). TXA is a synthetic amino acid that blocks plasminogen conversion to plasmin, to stabilize clot formation. The intravenous (IV) efficacy in reducing hematoma rates has been established in implant-based breast reconstruction, as well as in reduction mammaplasty. However, there are currently no studies investigating the use of IV TXA in patients undergoing GAM. The investigators propose a single-center, prospective randomized control trial to evaluate the efficacy and safety of intravenous tranexamic acid in decreasing hematoma and seroma rates for top surgery patients at UCSF. Patients will be randomized into two groups, an experimental group receiving IV TXA and a control group that will not receive IV TXA. Patients in the experimental group will receive a loading dose of tranexamic acid (TXA) at a concentration of 1g/10ml over a period of 10 minutes, administered immediately following anesthesia induction. Patients will be excluded if they have a history of coagulopathy, bleeding disorders or prior chest surgery. Demographic data, surgical characteristics, and postoperative outcomes will also be recorded and analyzed. The investigators hypothesize that the use of IV TXA will significantly reduce hematoma, seroma, postoperative drain output, and time to drain removal in patients undergoing GAM. Aim 1: To evaluate the effectiveness of IV TXA in reducing intraoperative bleeding, post-operative hematoma and seroma formation, drain output, and time to drain removal in patients undergoing GAM. Aim 2: To compare the incidence of thromboembolic events and wound complications between patients receiving IV TXA and those who do not after GAM.

Do I need to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anticoagulant or antiplatelet medications.

What data supports the effectiveness of the drug Tranexamic Acid (TXA) for gender-affirming mastectomy?

Research shows that Tranexamic Acid (TXA) can reduce postoperative complications like bleeding and fluid buildup in surgeries, including gender-affirming mastectomy and breast reduction. This suggests that TXA may help improve recovery by minimizing these issues. ^{1 2 3 4 5}

Is tranexamic acid (TXA) safe for use in surgeries?

Tranexamic acid (TXA) is generally considered safe for use in surgeries, as it has been shown to reduce blood loss and the need for blood transfusions in various procedures, including breast reduction and shoulder surgeries. Studies have not found an increased risk of complications, even in patients with a history of blood clots. ^{1 2 4 6 7}

How does the drug Tranexamic Acid (TXA) differ from other treatments for gender affirming mastectomy?

Tranexamic Acid (TXA) is unique in its use for gender affirming mastectomy as it helps reduce bleeding by preventing the breakdown of blood clots, which is different from other treatments that may focus on cancer or tumor management. This makes TXA particularly useful in surgeries to minimize blood loss, whereas other treatments like chemotherapy or radiation are aimed at treating cancerous conditions. ^{8 9 10 11 12}

Research Team

Esther Kim, MD

Principal Investigator

UCSF Department of Plastic & Reconstructive Surgery

Eligibility Criteria

This trial is for adults over 18 who are undergoing gender affirming mastectomy at UCSF and meet WPATH guidelines. It's not for those with a history of bleeding disorders, chest surgery, severe kidney issues, or allergies to TXA. Participants must be able to consent and should not have chronic anticoagulation or antiplatelet medication use.

Inclusion Criteria

I had a gender affirming mastectomy at UCSF.

I meet the WPATH standards for gender-affirming surgery, including hormone therapy and mental health stability.

ASA I-III

Exclusion Criteria

I take blood thinners regularly or have had a bad reaction to IV TXA.

I have a history of bleeding disorders or blood clotting issues.

I have had blood clots in my veins or lungs before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo gender affirming mastectomy with or without intravenous tranexamic acid (TXA) administration

1 day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for hematoma, seroma, and drain output; standard postoperative care is provided

Up to 3 months

Multiple visits (in-person)

Follow-up

Participants are monitored for long-term outcomes including thromboembolic events and wound complications

1 year

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview The study tests if intravenous tranexamic acid (IV TXA) can reduce bleeding and fluid collection after gender affirming mastectomy. Patients will be randomly assigned to receive IV TXA or no treatment in this prospective randomized control trial.

Participant Groups

Group I: IV TXA Group Experimental Treatment 1 Intervention

Patients in the experimental group will receive a loading dose of IV tranexamic acid (TXA) at a concentration of 1g/10ml over a period of 10 minutes, administered immediately following anesthesia induction. Postoperative care will be standard and based on established UCSF guidelines.

Group II: Control Group Active Control 1 Intervention

Patients in the control group will not receive any IV TXA intraoperatively and will undergo a traditional gender affirming mastectomy following the established standard of care.

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?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Findings from Research

In a study of 260 patients undergoing gender-affirming mastectomies, the periareolar technique was associated with a higher rate of hematomas (12.5% vs. 2.9%) and a greater need for revisionary surgery (15.0% vs. 5.2%) compared to the double-incision method, indicating potential complications with the periareolar approach.

The use of intraoperative liposomal bupivacaine (Exparel) significantly reduced opioid consumption during and after surgery, while the application of tranexamic acid (TXA) did not show any impact on reducing postoperative complications like hematomas or seromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of enhanced recovery protocols and tranexamic acid on double-incision versus periareolar gender-affirming mastectomy: A retrospective study of postoperative outcomes. Edalatpour, A., Seitz, AJ., Warden, AM., et al.[2023]

In a study of 81 patients undergoing breast reduction, the use of local tranexamic acid (TXA) did not significantly reduce intraoperative blood loss or operative time compared to standard procedures without TXA.

However, the TXA group experienced lower rates of T-junction dehiscence and suture granulomas, suggesting that TXA may enhance safety without increasing overall complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Infiltration of Tranexamic Acid in Breast Reduction for Symptomatic Macromastia. Nichols, G., Andrade, E., Gregoski, M., et al.[2023]

Intraoperative administration of tranexamic acid (TXA) during gender-affirming mastectomy significantly reduced the rates of postoperative seroma (20.5% vs. 33.0%) and hematoma (0.5% vs. 5.7%) compared to patients who did not receive TXA, based on a study of 851 patients.

The use of TXA did not increase the risk of venous thromboembolism or surgical-site infections, indicating that it is a safe option for minimizing blood loss and complications in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Tranexamic Acid in Gender-Affirming Mastectomy Reduces Rates of Postoperative Hematoma and Seroma. Rifkin, WJ., Parker, A., Bluebond-Langner, R.[2023]

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]

A systematic review of five studies involving 1139 patients showed that perioperative administration of tranexamic acid (TXA) significantly reduces the risk of hematoma (7.3% vs. 12.9%) and seroma formation (11.5% vs. 19.9%) in breast surgery.

The use of TXA did not increase the risk of thromboembolic events or postoperative infections, indicating it is a safe option for patients undergoing breast surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic Acid Use in Breast Surgery: A Systematic Review and Meta-Analysis. Liechti, R., van de Wall, BJM., Hug, U., et al.[2023]

Tranexamic acid (TXA) significantly reduces perioperative blood loss in total shoulder arthroplasty (TSA), with a notable decrease in hemoglobin change, drain output, and total blood loss, particularly after reverse TSA, based on a meta-analysis of 6 studies involving 680 patients.

While TXA shows a trend towards reducing transfusion rates after reverse TSA, it did not significantly affect transfusion rates after anatomic TSA, indicating a need for further research to clarify its efficacy in different TSA types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid administration for anatomic and reverse total shoulder arthroplasty: a systematic review and meta-analysis. Box, HN., Tisano, BS., Khazzam, M.[2022]

In a study of 71,174 shoulder arthroplasty patients, tranexamic acid (TXA) significantly reduced the need for blood transfusions without increasing the risk of complications, even in patients with a history of thrombotic events.

TXA use in patients with a history of thrombotic events was associated with a reduction in hospitalization costs, suggesting it is a safe and effective option for managing blood loss in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of tranexamic acid during total shoulder arthroplasty is not associated with increased risk of complications in patients with a history of thrombotic events. Carbone, A., Poeran, J., Zubizarreta, N., et al.[2021]

The combination of docetaxel and radiation therapy resulted in partial remission of metastatic tumors in a 68-year-old woman with recurrent breast cancer, indicating its potential efficacy for treating such cases.

Despite experiencing significant side effects like alopecia and neutropenia, the adverse reactions were manageable and reversible, suggesting that this treatment strategy can be safely administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of head metastases of breast cancer successfully treated with radiation therapy and docetaxel]. Aotake, T., Horiuchi, T., Yokomachi, J., et al.[2018]

In two cases of advanced metastatic breast cancer, the combination of docetaxel and intra-arterial adriamycin resulted in clinical responses lasting over 20 weeks, indicating potential efficacy of this treatment approach.

The therapy was associated with manageable side effects, including grade 2 leukopenia and alopecia, but no severe grade 4 toxicities, suggesting that it can be safely administered to outpatients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two cases of advanced and metastatic breast cancers treated by docetaxel in combination with intra-arterial infusion of adriamycin]. Doihara, H., Yoshitomi, S., Hino, M., et al.[2018]

Weekly administration of paclitaxel (80 mg/m2) was effective in treating metastatic breast cancer in two cases, leading to the disappearance of metastatic lymph nodes and lesions within 3 months.

The treatment was well-tolerated, with only mild toxic effects such as grade 1 leukopenia and peripheral neuropathy, indicating a favorable safety profile for outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two cases of effective weekly paclitaxel administration for metastatic breast cancer]. Kokufu, I., Taniguchi, H., Kim, Y., et al.[2015]

The study found that when paclitaxel (TXL) is conjugated to poly(L-glutamic acid) to form PG-TXL, its distribution to tumor tissue is significantly enhanced, with tumor exposure being five times greater compared to TXL administered in a conventional formulation.

PG-TXL maintains a consistent release of free paclitaxel within the tumor over time, which may contribute to its observed antitumor activity in preclinical studies, suggesting a promising mechanism for improving cancer treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor. Li, C., Newman, RA., Wu, QP., et al.[2017]

PG-TXL, a drug conjugate with polymeric carriers, significantly enhances the effectiveness of radiotherapy in treating ovarian tumors, reducing the radiation dose needed for tumor control by a factor of 7.2 for single doses and 8.4 for fractionated doses.

Importantly, PG-TXL does not increase damage to normal tissues during radiation treatment, suggesting it can improve the therapeutic ratio of radiotherapy without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(L-glutamic acid)-paclitaxel conjugate is a potent enhancer of tumor radiocurability. Milas, L., Mason, KA., Hunter, N., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes of enhanced recovery protocols and tranexamic acid on double-incision versus periareolar gender-affirming mastectomy: A retrospective study of postoperative outcomes. [2023]

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

Local Infiltration of Tranexamic Acid in Breast Reduction for Symptomatic Macromastia. [2023]

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

Use of Tranexamic Acid in Gender-Affirming Mastectomy Reduces Rates of Postoperative Hematoma and Seroma. [2023]

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

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

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

Tranexamic Acid Use in Breast Surgery: A Systematic Review and Meta-Analysis. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Tranexamic acid administration for anatomic and reverse total shoulder arthroplasty: a systematic review and meta-analysis. [2022]

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

Administration of tranexamic acid during total shoulder arthroplasty is not associated with increased risk of complications in patients with a history of thrombotic events. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

[A case of head metastases of breast cancer successfully treated with radiation therapy and docetaxel]. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

[Two cases of advanced and metastatic breast cancers treated by docetaxel in combination with intra-arterial infusion of adriamycin]. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

[Two cases of effective weekly paclitaxel administration for metastatic breast cancer]. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor. [2017]

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

Poly(L-glutamic acid)-paclitaxel conjugate is a potent enhancer of tumor radiocurability. [2019]