SEroma Reduction pOst MAstectomy "SEROMA Study" (SEROMA)

Pilot RCT: Use of Tranexamic Acid (TXA) in Post Mastectomy Patients for Seroma and Hematoma Prevention

This is a pilot study to evaluate the feasibility of conducting a larger trial to determine if the use of intraoperative topical tranexamic acid (TXA) decreases the rate of post-operative hematomas and seromas in breast cancer patients after their mastectomy. In other words, the investigators want to determine if applying TXA inside the surgical wound before it is closed helps reduce blood or serous fluid accumulation at the operative site. Dependent on the results of this study, a further larger trial may or may not take place.

Post-operative seromas and hematomas are common complications of mastectomy surgery not only leading to infection, discomfort, wound dehiscence or emergency room visits; they also delay in some instances post-operative adjuvant radiotherapy. Establishing whether or not topical TXA is an effective strategy to decrease those complications can potentially impact positively the breast cancer treatment.

To achieve this aim, this randomized pilot study will first determine whether a larger multicenter study if feasible. This study will replicate a formal randomized trial at a smaller scale in a single center in order to assess the recruitment and randomization process, as well as provide preliminary results for our research question.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Seroma Complicating A Procedure; Hematoma Postoperative
• Intervention / Treatment: Drug: Tranexamic Acid 100mg/mL, 20mL topical; Drug: Normal Saline Flush, 0.9%, 20mL topical

Detailed Description

The objective of this study is to investigate the novel use of topical application of Tranexamic Acid (TXA) to the surgical wound as a means to decrease seroma and/or hematoma formation compared to placebo in post-mastectomy patients. This project is designed as a single-center pilot RCT to evaluate the feasibility of conducting a formal RCT (multicenter trial including more patients) to evaluate the effectiveness of topical TXA.

Patients will be randomly assigned to one of two treatment groups for intraoperative treatment of their mastectomy wound before it is closed.

The first group will consist of those who will be treated with the intravenous form of TXA that will be applied to the surface of the mastectomy wound area rather than being injected into a vein. The second group consists of those individuals who will be treated with a topical normal saline solution (a placebo, or inactive substance that looks identical to the study drug but contains no therapeutic ingredients).

Both groups will receive the same number of drains and the same post-operative follow-up schedule consisting of visits 2 to 4 weeks and 3 months after the surgery, as well as a last 12 months follow-up. Standard of care will be practiced with respect to all procedures and visits.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Isabelle Duchesnay, M.D.; Phone Number: #4843 905-521-2100; Email: isabelle.duchesnay@medportal.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Juravinski Hospital - Hamilton Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Breast cancer diagnosis
• Age 18-80
• Fluent in English
• Female undergoing mastectomy with or without axillary intervention

Exclusion Criteria:

• Immediate reconstruction
• Pre-surgical radiation
• Known allergy to TXA
• Known thromboembolic disease
• High-risk of thromboembolism and/or receiving anticoagulants
• History of myocardial infarction (MI), transient ischemic attack or stroke within the last year
• History of subarachnoid hemorrhage
• Premenopausal women with irregular menstrual bleeding of unknown cause
• Acquired disturbances of colour vision
• Hematuria with renal cause
• History of seizure disorder
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo arm	Drug: Normal Saline Flush, 0.9%, 20mL topical; Drug: Normal Saline 20 mL 0.9% NaCl (normal saline) applied topically to the mastectomy cavity for 5 minutes before wound closure
Experimental: TXA arm	Drug: Tranexamic Acid 100mg/mL, 20mL topical; Drug: Tranexamic Acid 20 mL TXA (100 mg/mL injection solution, total 2g TXA) applied topically to the mastectomy cavity for 5 minutes before wound closure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Number of patients recruited over the total number of eligible patients screened	About 6 months
Randomization rate	Number of patients randomized over total number recruited	About 9 months
Follow-up visit rate	Number of patients with successful follow-up visits at 3 weeks and 3 months	3 months
Ability to adhere to protocol	Number of patients randomized to TXA who received TXA vs number of patients randomized to placebo who received the placebo	About 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroma rate	Rate of seroma formation within 3 months following mastectomy in each arm of the study.	3 months
Seroma volume	Amount of drainage (volume) in patients who did have a seroma, for patients in both arms of the study	3 months
Seroma aspiration	Aspirated volume in patients who did have a seroma, for patients in both arms of the study	3 months
Delay in adjuvant treatment	Time (number of weeks) of delay in adjuvant treatment due to seroma/hematoma complication, for patients in both arms of the study	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other complications rate: Hematoma rate	Rate of hematoma within 3 months following mastectomy in each arm of the study	3 months
Other complications rate: Infection rate	Rate of infection within 3 months following mastectomy in each arm of the study	3 months
Other complications rate: Wound dehiscence rate	Rate of wound dehiscence within 3 months following mastectomy in each arm of the study	3 months
Daily output volume	Daily drain output (volume), in patients in both arms of the study	3 months
Drain discontinuation	Time to drain discontinuation (number of days) in patients in both arms of the study	3 months
Drain complications	Presence of drain complications (leakage, dislodgement, blockage), in patients in both arms of the study	3 months
Safety outcomes: rate of thromboembolic events	Rate of Thromboembolic events within 3 weeks following mastectomy, in patients in both arms of the study	3 weeks
Safety outcomes: rate of myocardial events	Rate of myocardial events within 3 weeks following mastectomy, in patients in both arms of the study • Rate of other adverse events within 3 weeks following mastectomy	3 weeks
Safety outcomes: rate of other adverse events	Rate of other adverse events within 3 weeks following mastectomy, in patients in both arms of the study	3 weeks

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Nicole Hodgson, MD, MSc, FRCSC, Hamilton Health Sciences, McMaster University

Publications and helpful links

General Publications

• Porter KA, O'Connor S, Rimm E, Lopez M. Electrocautery as a factor in seroma formation following mastectomy. Am J Surg. 1998 Jul;176(1):8-11. doi: 10.1016/s0002-9610(98)00093-2.
• Coveney EC, O'Dwyer PJ, Geraghty JG, O'Higgins NJ. Effect of closing dead space on seroma formation after mastectomy--a prospective randomized clinical trial. Eur J Surg Oncol. 1993 Apr;19(2):143-6.
• Oertli D, Laffer U, Haberthuer F, Kreuter U, Harder F. Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer. Br J Surg. 1994 Jun;81(6):856-9. doi: 10.1002/bjs.1800810621.
• Pogson CJ, Adwani A, Ebbs SR. Seroma following breast cancer surgery. Eur J Surg Oncol. 2003 Nov;29(9):711-7. doi: 10.1016/s0748-7983(03)00096-9.
• van Bemmel AJ, van de Velde CJ, Schmitz RF, Liefers GJ. Prevention of seroma formation after axillary dissection in breast cancer: a systematic review. Eur J Surg Oncol. 2011 Oct;37(10):829-35. doi: 10.1016/j.ejso.2011.04.012. Epub 2011 Aug 17.
• Baker E, Piper J. Drainless mastectomy: Is it safe and effective? Surgeon. 2017 Oct;15(5):267-271. doi: 10.1016/j.surge.2015.12.007. Epub 2016 Feb 19.
• He XD, Guo ZH, Tian JH, Yang KH, Xie XD. Whether drainage should be used after surgery for breast cancer? A systematic review of randomized controlled trials. Med Oncol. 2011 Dec;28 Suppl 1:S22-30. doi: 10.1007/s12032-010-9673-2. Epub 2010 Sep 9.
• Ker K, Roberts I, Shakur H, Coats TJ. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev. 2015 May 9;(5):CD004896. doi: 10.1002/14651858.CD004896.pub4.
• Gupta K, Rastogi B, Krishan A, Gupta A, Singh VP, Agarwal S. The prophylactic role of tranexamic acid to reduce blood loss during radical surgery: A prospective study. Anesth Essays Res. 2012 Jan-Jun;6(1):70-3. doi: 10.4103/0259-1162.103378.
• Perel P, Ker K, Morales Uribe CH, Roberts I. Tranexamic acid for reducing mortality in emergency and urgent surgery. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD010245. doi: 10.1002/14651858.CD010245.pub2.
• Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013 Jul 23;(7):CD010562. doi: 10.1002/14651858.CD010562.pub2.
• Xu X, Xiong S, Wang Z, Li X, Liu W. Topical administration of tranexamic acid in total hip arthroplasty: A meta-analysis of Randomized Controlled Trials. Drug Discov Ther. 2015 Jun;9(3):173-7. doi: 10.5582/ddt.2015.01018.
• 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.
• Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2014 Nov 21;2014(11):CD006640. doi: 10.1002/14651858.CD006640.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; tranexamic acid; topical; mastectomy; seroma; hematoma
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Hemorrhage; Hematoma; Seroma; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 5271

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No