Tranexamic Acid Usage in Bilateral Mastectomy to Reduce Post-surgical Drainage

Sponsor

Northwestern University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05554211

Collaborator

Saint Joseph Hospital, Chicago, Illinois (Other), Northwestern Memorial Hospital (Other)

Enrollment

Locations

Arms

11.6

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Tranexamic acid (TxA) is a drug that was approved by the FDA in 1986. It is an antifibrinolytic drug - this means that it is used to promote blood clotting by preventing the breakdown of blood clots that your body naturally forms. TxA is very commonly used to control bleeding in a variety of surgeries, such as orthopedic and gynecologic procedures, and is available in both the injectable (delivering the drug through the veins) and oral forms. However, its use is still not commonplace in the setting of elective breast surgery, because it hasn't been extensively studied in this field. Because it is not currently FDA-approved for use in elective breast surgery, this would make the drug "investigational" for this study. Because of its current use in other fields, TxA seems to have a great deal of potential in reducing the amount of post-operative time that breast drains need to be kept in place, the frequency of adverse events during wound healing such as bleeding and fluid accumulation, and overall fluid drainage amount. This would serve to improve the overall process of post-operative healing following a mastectomy procedure. Currently, the use of TxA is approved through the injectable route at Northwestern, but it is not approved for administration by the topical route. Previous studies have shown that TxA given through the topical route of administration in breast reduction surgery reduced post-surgical drainage and fluid accumulation. In this study, we'll be investigating the use of 3% (3 grams of TxA in 100 ml of saline) TxA through the topical route by applying it to the breast wound of one breast as a direct fluid irrigation. This will be done as a fluid wash, where the TxA will be in a syringe, and just before wound closure the TxA will be sprayed onto the wound site. The other breast will undergo the same procedure, but will receive normal saline solution instead of TxA. The procedure of interest here is a prophylactic bilateral mastectomy, which is a mastectomy that is performed to prevent the occurrence of breast cancer. The purpose of this study is to test whether applying TxA topically during wound closure in mastectomy procedures will affect the quantity of fluid accumulation and bleeding, and the amount of time that post-operative drains need to be kept in place.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer BRCA Mutation	Drug: Tranexamic acid Drug: Normal saline	Phase 2

Detailed Description

Breast cancer is the second most common cancer among women in the United States. Mastectomy procedures are often performed to treat breast cancer, and may either be done prophylactically or therapeutically. Women with either a strong family history of breast cancer and/or a positive mutation for BRCA1 or BRCA2 may elect to undergo a prophylactic mastectomy, in which one or both breasts are removed. Such procedures have been found to reduce the risk of developing breast cancer in these individuals by 90-95%. This process often begins with an individual who has a family member or relative that has tested positive for a BRCA mutation or developed breast cancer. Female family members may then choose to undergo screening to identify whether they carry such a genetic mutation themselves, and if any family member screens positive for the mutation, one may solicit a plastic surgeon for the mastectomy to prevent future breast cancer occurrence. Additionally, women may elect to undergo a mastectomy after the development of cancer in one or both breasts. In the event of cancer development in one breast, patients may choose to undergo a bilateral mastectomy therapeutically in the breast with cancer and prophylactically in the breast without cancer to prevent future cancer development in the non-cancer breast.

During mastectomy procedures, tumescent solution is commonly used for regional anesthesia and reduction of blood loss through potent vasoconstriction. Tumescent solution is an infiltration solution (a formula consisting of epinephrine, lidocaine in Lactated Ringer's solution diluted in saline) that usually contains 0.05% lidocaine and 1:1,000,000 epinephrine. While there are several studies investigating various modified recipe of tumescent solution during BRRM with the goal of reducing perioperative bleeding, the results remain inconsistent.

In this study, we investigate the use of TxA in bilateral mastectomy in a cohort of female patients. TxA is an anti-fibrinolytic agent commonly used to control trauma and menstrual bleeding, as well as in routine surgical procedures. In prior studies, TxA has been shown to reduce mortality due to adverse bleeding events by one-third1. In addition, TxA mechanism-of-action has been shown to exert an immunomodulatory effect that results in reduced infection rates independent of its effect on reduction of blood loss4. Because of this, TxA has become an attractive agent for use in surgery to control bleeding during procedures and post-surgical fluid accumulation at the wound site. However, its use is still not commonplace in the setting of elective breast surgery.

During breast surgery, agents such as tumescent solution are commonly administered to reduce peri-operative bleeding and post-surgical blood and fluid accumulation. Following surgery, drainage systems such as Jackson-Pratt drains are placed within the breast to allow for fluid removal and prevent the incidence of infection, hematoma, and seroma. To date, few studies have investigated the perioperative use of TxA during breast surgery to reduce post-surgical fluid drainage and reduction of corresponding adverse events - as a result, we believe that there is a great deal of potential in this investigation to inform future surgical practices in this field and to improve patients' quality-of-life. In this study, we will conduct a prospective study of female patients undergoing bilateral mastectomy to determine the effect of TxA administration in reducing post-surgical breast drainage and indwelling time and preventing adverse fluid accumulation-related events.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In a within-subjects design, one breast will receive normal saline control and the contralateral breast will receive tranexamic acid.In a within-subjects design, one breast will receive normal saline control and the contralateral breast will receive tranexamic acid.

Masking:

Single (Investigator)

Masking Description:

Each solution (topical saline irrigation vs. TxA) will be prepared by the hospital pharmacy on the day of the procedure and given a blinded code number so that the surgeons and study's investigators will be blinded to which breast received which solution. A randomization table will be used to determine whether the right or left breast receives TxA for each patient. Each wound, whether treated with the control agent of TxA, will be irrigated with gentamicin. The labeling and volume of both the TxA and control irrigation syringes will be visually identical for blinding purposes with the exception of the label indicating whether the syringe is for the "right" or "left" breast. Two pharmacy staff members will check the breast assignment on the label against the randomization table. Each label will contain the patient's subject ID number and the study protocol number.

Primary Purpose:

Treatment

Official Title:

Tranexamic Acid Usage in Bilateral Mastectomy to Reduce Post-surgical Drainage

Actual Study Start Date :

Jul 12, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Breast Participants will receive 50 ml of TxA and gentamicin to the assigned experimental breast.	Drug: Tranexamic acid The intervention is a topical application of 50 cc's of 3% tranexamic acid. In the operating room, TxA irrigation will be administered following gentamicin irrigation. TxA irrigation solution will be the last irrigation used prior to wound closure in order to assure maximum benefit derived from TxA administration, if any.
Placebo Comparator: Control Breast Participants will receive a standard irrigation of 50 ml of 0.9% NS and gentamicin to the assigned control breast.	Drug: Normal saline The intervention is a topical application of 50 cc's of 3% tranexamic acid. In the operating room, control NS irrigation will be administered following gentamicin irrigation. NS irrigation solution will be the last irrigation used prior to wound closure in order to assure maximum benefit derived from TxA administration, if any.

Arm

Intervention/Treatment

Experimental: Experimental Breast

Participants will receive 50 ml of TxA and gentamicin to the assigned experimental breast.

Drug: Tranexamic acid

The intervention is a topical application of 50 cc's of 3% tranexamic acid. In the operating room, TxA irrigation will be administered following gentamicin irrigation. TxA irrigation solution will be the last irrigation used prior to wound closure in order to assure maximum benefit derived from TxA administration, if any.

Placebo Comparator: Control Breast

Participants will receive a standard irrigation of 50 ml of 0.9% NS and gentamicin to the assigned control breast.

Drug: Normal saline

The intervention is a topical application of 50 cc's of 3% tranexamic acid. In the operating room, control NS irrigation will be administered following gentamicin irrigation. NS irrigation solution will be the last irrigation used prior to wound closure in order to assure maximum benefit derived from TxA administration, if any.

Outcome Measures

Primary Outcome Measures

Drain output [Approximately 1 month post-operatively]
The primary clinical endpoints in this study are the post-surgical drainage volume and drainage system indwelling time. Each drainage system will be removed post-operatively when the drainage amount is equal to or less than 30cc's for two consecutive 24-hour periods. Additionally, observations will be made regarding the post-surgical fluid accumulation, such as hematoma and seroma formation, and characterization of the fluid (bloody, purulent, serosanguinous, etc.)

Secondary Outcome Measures

Safety evaluation [Approximately 1 month post-operatively]
The primary safety endpoint will be the development of previously noted side effects in studies of TxA usage - primarily headache, diarrhea and nausea predominantly associated with oral administration of TxA - as self-reported by the particpants of those studies. Incidence of all side effects will be monitored.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Female aged 18 years or older
Scheduled or plans to schedule a bilateral mastectomy
Able to understand informed consent and sign it voluntarily

Exclusion Criteria:

Male without breasts
Females who have previously undergone either unilateral or bilateral mastectomy as they do not have breasts on which the drug could be tested
Patients with a hypersensitive or allergic reaction to TxA
Patients with an active clotting disorder
Patients with a subarachnoid hemorrhage within the past 3 months of screening
Patients on chronic, extracorporeal renal replacement therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
2	AMITA Health Saint Joseph Chicago	Chicago	Illinois	United States	60657

Sponsors and Collaborators

Northwestern University
Saint Joseph Hospital, Chicago, Illinois
Northwestern Memorial Hospital

Investigators

Principal Investigator: Robert L Walton, MD, Northwestern Feinberg School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Robert Walton, Clinical Professor of Plastic Surgery, Northwestern University

ClinicalTrials.gov Identifier:

NCT05554211

Other Study ID Numbers:

STU00214745

First Posted:

Sep 26, 2022

Last Update Posted:

Sep 26, 2022

Last Verified:

Sep 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Robert Walton, Clinical Professor of Plastic Surgery, Northwestern University

mastectomy

tranexamic acid

Additional relevant MeSH terms:

Tranexamic Acid

Study Results

No Results Posted as of Sep 26, 2022