Tranexamic Acid for Bleeding in Breast Surgery (TABBS)

January 11, 2016 updated by: Ottawa Hospital Research Institute

Minimization of Bleeding Complications Through Utilization of Perioperative Tranexamic Acid in Breast Surgery: A Randomized Double-blinded Placebo-controlled Trial

Bleeding is an important consideration in breast surgeries that involve large resections of soft tissues in the breast. Inappropriate bleeding during or after surgery, can lead to uncomfortable fluid buildup in the breasts known as a hematoma or seroma, which may require additional procedures or reoperation. Patients may experience a great deal of discomfort and additional costs as a result; additional hospital time and procedures also burdens health care spending. Tranexamic acid (TXA) is commonly used drug in many medical settings to reduce excessive bleeding; however, no such drug is standard practice in breast surgery. The aim of this study is to determine if TXA is superior to placebo in reducing the bleeding complications in breast surgeries, including reduction mammaplasty, mastectomy with and without immediate tissue expander and implant-based reconstruction, and oncoplastic breast surgery. This study is a randomized, double-blind, placebo-controlled trial. Patients undergoing these procedures will be randomly allocated to receive either TXA or placebo. Patients will be placed on a drug/placebo regimen of 3 doses/day for 6 days starting on the day of their surgery. The primary outcome is the incidence of hematoma and/or seroma formation following breast surgery. Cost analysis of the intervention will also be performed.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background:

Aberrant bleeding is an important consideration in breast surgery, which can involve large resections of soft tissues in the breasts. Hematomas and/or seromas are common complications with these procedures, and can lead to further complications, such as flap necrosis. Seromas, perhaps the commonest complication, are documented to occur at rates as high as 85% in certain breast procedures. Hematoma rates are typically lower than that of seroma, ranging from 1% to 2% in mastectomy procedures and 5% to 8% in reduction mammaplasty. These bleeding complications pose an obvious risk to patient safety, and their management can result in significant costs to patients and healthcare alike.

Tranexamic acid (TXA), also known by the brand name Cyklokapron® from Pfizer™, is a lysine analogue used to prevent and/or treat bleeding by competitively blocking the activation of plasminogen to plasmin, thereby preventing plasmin from binding to blood clots. Tranexamic acid is used safely in several medical and surgical settings, such as cone biopsies, epistaxis and hyphaema control, and dental surgery. This antifibrinolytic medication is commonly used in many surgical procedures, namely cardiac and orthopedic surgery, for the purposes of preventing blood loss. TXA has been demonstrated to effectively reduce perioperative blood loss and transfusion rates in many different surgical procedures, such as cardiac, urology, gynecology, and orthopedic surgeries, without any significant safety concerns.

Despite these findings, there is a clear paucity of studies on TXA in breast surgery. There are currently no studies exploring perioperative TXA use in breast reduction, and only one study in breast surgery overall. This study by Oertli et al. looked at the use of TXA in mastectomy or lumpectomy with axial dissection, in a randomized placebo-controlled trial (RCT). Seroma rate was shown to be reduced by 10% with a reduction in TXA versus placebo. However, due to a low power of the study, Oertli et al. were unable to determine statistical significance.

Purpose:

The purpose of this study is to determine if perioperative administration of tranexamic acid (TXA) is superior to placebo in minimizing bleeding complications (as determined by: hematoma/seroma incidence in the breast, re-operation and/or additional procedures, blood transfusion volume, drainage volume (Jackson-Pratt drain or percutaneous drainage), number of days spent in hospital) in breast surgery (Reduction mammaplasty, mastectomy with and without immediate tissue expander and implant-based reconstruction, oncoplastic breast surgery). Conterminous with this objective, the investigators also intend to study the safety of tranexamic acid use perioperatively in these procedures by recording any adverse effects that occur at the time of surgery and throughout the follow-up period. The study will randomize and prospectively observe two patient populations undergoing any one of these procedures: one group receiving preoperative and subsequent post-operative 1g doses of tranexamic acid, and the other receiving placebo (normal saline). These two groups will be observed based on specific properties and complications from surgery. Finally, to determine if perioperative TXA use is more cost-effective than placebo in the setting of breast surgery. Information on health care utilization will be collected prospectively in both groups to provide a cost analysis of tranexamic acid.

The following hypotheses will be tested:

  1. Perioperative TXA use is superior to placebo in reducing bleeding complications (ie. hematoma, seroma, and excessive blood loss) in the surgical or donor site.
  2. Perioperative TXA is safe for use in this patient population.

Study Design

The present study will be a randomized, double-blind, placebo-controlled trial. This RCT will follow the CONSORT statement. Conterminous to this RCT, data on treatment costs (hospital and patient cost) will be recorded. The study will last approximately two years. Case Report Forms will be filled out at each follow-up period. Follow-up will occur at 2 weeks, 6 weeks, and 12 weeks postoperatively. Cost-analysis of the intervention will also be performed.

Sample Size:

Based on published data, the incidence of the combined hematoma/seroma endpoint is expected to range between 6 and 10% in the reductions patients and 16-87% in the mastectomy patients. Since the investigators expect to have equal numbers of each type of patient, the investigators anticipate the overall event rate in the placebo arm to range between 11-47%. Taking the midpoint, the investigators anticipate a placebo arm event rate of 29%. The investigators would consider a 30% relative reduction (i.e., an absolute difference of 9%) to be the minimal clinically important difference that would, if demonstrated, change practice. To detect this difference with 80% power, the investigators require 385 patients per arm using a two-sided test at the 5% level of significance To account for attrition of 15 patients per arm (<5%), the investigators will aim to 400 patients per group.

Data Analysis:

The unit of analysis will be each individual patient for all outcomes. Baseline characteristics will be compared between study arms using descriptive statistics (frequencies and proportions for categorical variables, mean and standard deviation for continuous variables with a normal distribution and median and inter-quartile range for variables with a skewed distribution). The investigators' primary outcome, the incidence of hematoma and/or seroma, will be analyzed using a chi-square test with continuity correction. The difference between the arms will be described using a relative risk with 95% confidence interval. The overall rate in each group will also be reported. Secondary outcomes will be analyzed using chi-square tests (dichotomous outcomes) or Wilcoxon tests (drainage volume, transfusion volume, and days in hospital). Drainage and transfusion volume, as well as the number of days in hospital, will be summarized as median and interquartile range. All data analysis will be carried out by a statistician from the Ottawa Hospital Research Institute.

Study Type

Interventional

Enrollment (Anticipated)

800

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patient requires and is a candidate for any of the following surgical procedures: Reduction mammaplasty, mastectomy with and without immediate tissue expander and implant-based reconstruction, oncoplastic breast surgery.
  • Patient has OHIP approval for surgery.
  • Patient is willing and able (ie. English/French-speaking and cognitively intact) to read and complete patient diaries, demographic forms, and consent forms and be followed-up for a 2 weeks, 6 weeks, 12 weeks postoperatively.
  • Patient is 18 years of age or older

Exclusion Criteria:

  • Patient is allergic to tranexamic acid
  • Patient has a history or present laboratory signs of bleeding disorders (abnormal platelet counts, prothrombin time, partial thromboplastin time, etc.), coagulopathy or thromboembolic events
  • Patient is being treated for a stroke
  • Patient has a history of bleeding in the brain
  • Patient has an acquired disturbance of colour vision
  • Patient has a history of myocardial infarction within the last year
  • Patient is presenting with unstable angina or severe coronary disease
  • Patient has reduced renal function with plasma creatinine levels above 250 umol/L ix.
  • Patient has haematuria
  • Patient is currently using a form of birth control that contains estrogen and a progestin
  • Patient has irregular menstrual bleeding of unknown cause
  • Patient is unable to complete required forms due to language and cognitive problems
  • Patient is not capable of communicating in, and understanding, English or French
  • Patient is currently pregnant and is expected to be pregnant during any point of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tranexamic Acid
Tranexamic acid will be provided as an intravenous infusion (1g in 100mL 0.9% NaCl solution [1% TXA] at 5 ml/min) 20 minutes pre-operatively, followed by an additional intravenous dose of the same dosing parameters postoperatively. Oral tablet doses containing 1 g of TXA (2x 500mg tablets) per dose will be administered to the patient to be taken orally by the patient according to a standard regimen; the first tablet dose will be taken on the same day as the surgery, in the evening. The patient will then take one tablet dose three times a day for a total of five days following the surgery (one dose in the morning, one dose mid-day, and one dose in the afternoon) for a 6 day total regimen.
Drug: Tranexamic Acid
Other Names:
  • Cyklokapron
Placebo Comparator: Placebo Control
Placebo control will be either 100 ml of 0.9% NaCl solution or tablets of similar appearance containing no medicinal ingredients; placebo will be administered according to the same regimen as the intervention group.
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of hematoma or seroma formation in breast surgical site as assessed by clinical examination.
Time Frame: 12 weeks following the operation
Hematoma or seroma formation in the breast surgical site(s) will be identified by surgeon on clinical examination during patient follow-up within 12 weeks post-operatively.
12 weeks following the operation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tranexamic Acid Adverse Events:
Time Frame: 12 weeks following the operation
Includes allergic and/or anaphylactic reactions, eye or eyesight problems, thromboembolic events, diarrhoea, gastrointestinal problems, hypersensitivity reactions, nausea and vomiting
12 weeks following the operation
Drainage volume as measured from Jackson-Pratt drain or percutaneous drainage
Time Frame: 12 weeks following the operation
12 weeks following the operation
Blood transfusion volume
Time Frame: During surgical operating time, during post-operative hospital admission time (1-7 days on average).
During surgical operating time, during post-operative hospital admission time (1-7 days on average).
Incidence of secondary breast operation
Time Frame: 12 weeks following the operation
Surgical revision of initial breast procedure due to unsatisfactory results
12 weeks following the operation
Incidence of additional procedures following initial breast operation to address hematoma or seroma
Time Frame: 12 weeks following the operation
Operative or non-operative procedures to correct hematoma or seroma in the breast surgical site
12 weeks following the operation
Number of days spent in hospital
Time Frame: 12 weeks following the operation
12 weeks following the operation
Cost associated with bleeding complications
Time Frame: 12 weeks following the operation
Additional cost of original procedure (including material costs, as well as OR time, surgeon, anesthetist, and nurse costs), cost per day spent in hospital, cost for additional care (including procedures, medication, etc.), patient/caregiver out-of-pocket expenses (dressings and medications, parking, transportation, days missed from work)
12 weeks following the operation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Hospital Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Anticipated)

February 1, 2019

Study Completion (Anticipated)

February 1, 2019

Study Registration Dates

First Submitted

November 17, 2015

First Submitted That Met QC Criteria

November 25, 2015

First Posted (Estimate)

November 26, 2015

Study Record Updates

Last Update Posted (Estimate)

January 12, 2016

Last Update Submitted That Met QC Criteria

January 11, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20150264-01H

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hematoma

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe