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

NCT05554211 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: STU00214745
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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 the participant's 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, 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 will be investigated. 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.

Conditions

Breast Cancer; BRCA Mutation

Keywords

mastectomy; tranexamic acid

Outcome Measures

Primary Outcomes (1)

• Drain output

  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.)

  Approximately 1 month post-operatively

Secondary Outcomes (1)

• Safety evaluation

  Approximately 1 month post-operatively

Study Arms (2)

Experimental Breast

EXPERIMENTAL

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

Drug: Tranexamic acid

Control Breast

PLACEBO COMPARATOR

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

Drug: Normal saline

Interventions

Tranexamic acid DRUG

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.

Experimental Breast

Normal saline DRUG

The intervention is a topical application of 50 cc's of 3% tranexamic acid. In the operating room, control normal saline (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.

Control Breast

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Saint Joseph Hospital, Chicago, Illinois: collaborator
• Northwestern Memorial Hospital: collaborator

Study Sites (2)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

AMITA Health Saint Joseph Chicago

Chicago, Illinois, 60657, United States

Location

Related Publications (19)

• Hunt BJ. The current place of tranexamic acid in the management of bleeding. Anaesthesia. 2015 Jan;70 Suppl 1:50-3, e18. doi: 10.1111/anae.12910.

  PMID: 25440395 BACKGROUND

• Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. doi: 10.2165/00003495-199957060-00017.

  PMID: 10400410 BACKGROUND

• McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012 Mar 26;72(5):585-617. doi: 10.2165/11209070-000000000-00000.

  PMID: 22397329 BACKGROUND

• Draxler DF, Yep K, Hanafi G, Winton A, Daglas M, Ho H, Sashindranath M, Wutzlhofer LM, Forbes A, Goncalves I, Tran HA, Wallace S, Plebanski M, Myles PS, Medcalf RL. Tranexamic acid modulates the immune response and reduces postsurgical infection rates. Blood Adv. 2019 May 28;3(10):1598-1609. doi: 10.1182/bloodadvances.2019000092.

  PMID: 31126915 BACKGROUND

• Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD, Orser BA. Tranexamic acid-associated seizures: Causes and treatment. Ann Neurol. 2016 Jan;79(1):18-26. doi: 10.1002/ana.24558. Epub 2015 Dec 15.

  PMID: 26580862 BACKGROUND

• Myckatyn TM, Tenenbaum MM. Discussion: Intravenous Tranexamic Acid in Implant-Based Breast Reconstruction Safely Reduces Hematoma without Thromboembolic Events. Plast Reconstr Surg. 2020 Aug;146(2):246-247. doi: 10.1097/PRS.0000000000006975. No abstract available.

  PMID: 32740568 BACKGROUND

• Weissler JM, Banuelos J, Jacobson SR, Manrique OJ, Nguyen MT, Harless CA, Tran NV, Martinez-Jorge J. Intravenous Tranexamic Acid in Implant-Based Breast Reconstruction Safely Reduces Hematoma without Thromboembolic Events. Plast Reconstr Surg. 2020 Aug;146(2):238-245. doi: 10.1097/PRS.0000000000006967.

  PMID: 32740567 BACKGROUND

• King, I. C., Mellington, A. J., Hazari, A., & Jones, M. E. (2019). Does tranexamic acid increase the risk of thromboembolic events in immediate or delayed breast reconstruction? A review of the literature. European Journal of Plastic Surgery, 42(6), 559-562. https://doi.org/10.1007/s00238-019-01527-9

  BACKGROUND

• Peitsidis P, Kadir RA. Antifibrinolytic therapy with tranexamic acid in pregnancy and postpartum. Expert Opin Pharmacother. 2011 Mar;12(4):503-16. doi: 10.1517/14656566.2011.545818. Epub 2011 Feb 4.

  PMID: 21294602 BACKGROUND

• Jules-Elysee KM, Tseng A, Sculco TP, Baaklini LR, McLawhorn AS, Pickard AJ, Qin W, Cross JR, Su EP, Fields KG, Mayman DJ. Comparison of Topical and Intravenous Tranexamic Acid for Total Knee Replacement: A Randomized Double-Blinded Controlled Study of Effects on Tranexamic Acid Levels and Thrombogenic and Inflammatory Marker Levels. J Bone Joint Surg Am. 2019 Dec 4;101(23):2120-2128. doi: 10.2106/JBJS.19.00258.

  PMID: 31800425 BACKGROUND

• Weissmann KA, Lafage V, Barrios Pitaque C, Lafage R, Descazeaux FM. Efficacy of topical versus intravenous tranexamic acid in spinal deformity. Eur Spine J. 2020 Dec;29(12):3044-3050. doi: 10.1007/s00586-020-06572-8. Epub 2020 Aug 31.

  PMID: 32869162 BACKGROUND

• https://www.breastcancer.org/treatment/surgery/prophylactic_mast

  BACKGROUND

• Ausen K, Fossmark R, Spigset O, Pleym H. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty. Br J Surg. 2015 Oct;102(11):1348-53. doi: 10.1002/bjs.9878.

  PMID: 26349843 BACKGROUND

• Ausen K, Hagen AI, Ostbyhaug HS, Olafsson S, Kvalsund BJ, Spigset O, Pleym H. Topical moistening of mastectomy wounds with diluted tranexamic acid to reduce bleeding: randomized clinical trial. BJS Open. 2020 Apr;4(2):216-224. doi: 10.1002/bjs5.50248. Epub 2019 Dec 26.

  PMID: 32207575 BACKGROUND

• Ausen K, Pleym H, Liu J, Hegstad S, Nordgard HB, Pavlovic I, Spigset O. Serum Concentrations and Pharmacokinetics of Tranexamic Acid after Two Means of Topical Administration in Massive Weight Loss Skin-Reducing Surgery. Plast Reconstr Surg. 2019 Jun;143(6):1169e-1178e. doi: 10.1097/PRS.0000000000005620.

  PMID: 31136475 BACKGROUND

• Uslu AB. Effect of Tumescent Lidocaine and Epinephrine Infiltration on Blood Loss in Inferior Pedicle Wise-Pattern Breast Reduction: A Prospective Randomized Study. Aesthetic Plast Surg. 2021 Apr;45(2):442-450. doi: 10.1007/s00266-020-01859-z. Epub 2020 Jul 15.

  PMID: 32671449 BACKGROUND

• https://www.cdc.gov/cancer/breast/statistics/index.htm

  BACKGROUND

• Chauncey JM, Wieters JS. Tranexamic Acid. [Updated 2021 Jul 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532909/

  BACKGROUND

• Hadad E, Wiser I, Rosenthal A, Landau G, Ziv E, Heller L. Suction drains in esthetic breast implant exchange are associated with surgical site infections: A retrospective cohort study. J Plast Reconstr Aesthet Surg. 2017 Nov;70(11):1635-1640. doi: 10.1016/j.bjps.2017.06.034. Epub 2017 Jul 6.

  PMID: 28781210 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tranexamic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Robert L Walton, MD

  Northwestern Feinberg School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 21, 2022
• First Posted: September 26, 2022
• Study Start: July 12, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: February 21, 2025

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)