Tranexamic Acid in Knee Joint Surgery (TRACKS)

May 12, 2020 updated by: Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS

Tranexamic Acid in Knee Joint Surgery - a Randomised Controlled Trial

Total knee joint replacement surgery can lead to significant blood loss, which can affect recovery after surgery. Tranexamic acid (TXA) is a medication which stops the breakdown of blood clots and therefore prevents blood loss. The optimal use of TXA remains a point of debate. Growing interest in the topical application of TXA (directly into the surgical wound) has been suggested as an alternative way of administering TXA, and may demonstrate similar effectiveness as when it is given intravenously. Therefore, this multicentred, randomized controlled trial, aims to investigate the safety and effectiveness of both topical and intravenous administrations of TXA in total knee joint surgery. The investigators predict that both routes of administration will demonstrate similar results when compared to placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Postoperative anaemia following elective arthroplasty can lead to prolonged hospital stay, delays in rehabilitation and is often poorly tolerated in patients with cardiovascular disease.(1) Tranexamic acid (TXA) in arthroplasty is used by many orthopaedic surgeons to reduce perioperative blood loss and subsequent transfusion of blood products in elective total hip and knee arthroplasty (THA and TKA). In several reviews, systemic TXA (sTXA) significantly reduces blood loss and transfusion rates when compared to placebo, without an increased risk for venous thromboembolism (VTE).(2-4)

The CRASH-2 study, with over 20,000 randomised trauma patients, has also confirmed the efficacy and safety of TXA in this setting, particularly when given early.(5) The evidence for its use to date is overwhelming and when not contraindicated, should be employed by all arthroplasty units as part of their standard practice. However, despite the vast evidence for its use in arthroplasty some surgeons remain cautious over its safety profile when given systemically. TXA is a synthetic derivative of lysine which is responsible for binding reversibly to plasminogen effectively inhibiting clot degradation.(6) Although, this is not clot promoting, inhibiting clot breakdown theoretically may increase the likelihood of clot formation. This is of real concern for surgeons in patients who have had previous VTE. For this reason, some surgeons have utilised TXA as a topical application directly into the surgical field to reduce systemic absorption and avoid VTE.(7, 8)

TXA administered topically in TKA has also been reported to reduce swelling which may have the advantage of earlier mobility and less pain.(9) In cardiac surgery, TXA has been touted as not only having blood conserving properties via the coagulation pathway but also reduces inflammation via attenuation of the pro-inflammatory cascade.(10, 11)

Based on this rationale, this appears to be a sensible and reasonable route of administration for TXA in this population. However, surgeons should ensure they avoid placing undue risk on patients by altering their use of TXA given the strong evidence for sTXA. Therefore, the purpose of this study is to assess whether topical TXA is effective in reducing blood loss in knee joint replacement surgery, and is as safe and as effective as systemic TXA.

Study Type

Interventional

Enrollment (Actual)

150

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.

Study Locations

  • New Zealand
      • Auckland, New Zealand
        • North Shore Hospital
      • Auckland, New Zealand
        • Auckland Hospital
      • Auckland, New Zealand
        • Manukau Surgery Centre
      • Nelson, New Zealand
        • Nelson Hospital
      • Tauranga, New Zealand
        • Tauranga Hospital

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

All

Description

Inclusion Criteria:

  • All patients at the participating sites on the waiting list for a unilateral total knee joint replacement

Exclusion Criteria:

  • Patients with a history or risk of thrombosis
  • Active thromboembolic disease such as deep vein thrombosis, pulmonary embolism and cerebral thrombosis
  • Subarachnoid haemorrhage
  • Hypersensitivity to tranexamic acid or any of its ingredients.
  • Refusal of blood products
  • Colour blindness
  • Complex hematologic disorders requiring manipulation
  • Coagulopathy
  • Pregnant and Lactating Women
  • Anti-coagulant therapy pre-operatively within 5 days of surgery (warfarin, dabigatran, heparin)
  • Severe renal failure (eGFR <29)

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis and left to sit for two minutes, excess carefully suctioned followed by standard closure with no drains; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Drug: Normal saline (0.9% NaCl)
Administered in all 3 groups
Other Names:
  • Normal saline
Experimental: Topical
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis with excess carefully suctioned followed by standard closure with no drains; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet.
Drug: Normal saline (0.9% NaCl)
Administered in all 3 groups
Other Names:
  • Normal saline
Drug: Tranexamic Acid
Given intravenously or topically
Other Names:
  • Cyclokapron
Experimental: Systemic
Application of 20ml of normal saline topically after implantation of prosthesis with excess carefully suctioned followed by standard closure with no drains; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet
Drug: Normal saline (0.9% NaCl)
Administered in all 3 groups
Other Names:
  • Normal saline
Drug: Tranexamic Acid
Given intravenously or topically
Other Names:
  • Cyclokapron

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Loss
Time Frame: Post operative day 3

The loss of haemoglobin (Hb) was then estimated according to the formula:

Hb(loss) = Blood volume (BV) x (Hbi-Hbe) x 0.001+Hbt

where Hb (loss) (g) is the amount of Hb lost, Hbi (g/L) the Hb concentration before surgery, Hbe (g/L) is the Hbe concentration on the third day after surgery, and Hbt (g) is the total amount of allogeneic Hb transfused. A unit of banked blood is considered to contain a minimum of 40g Hb (Blood component data sheet, New Zealand Blood Services [NZBS]). All units of blood are processed and stored in a nationally standardised manner. The blood loss (ml) was related to the patient's preoperative Hb value (g/L):

Blood loss =1000 x Hb(loss) /Hbi
Post operative day 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Symptomatic Venothromboembolic (VTE) Disease
Time Frame: Postoperatively within 30 days after surgery
Rates of deep vein thrombosis (DVT) and pulmonary embolus (PE) in each group recorded as a percentage
Postoperatively within 30 days after surgery
Number of Participants Receiving Allogenic Blood Transfusion
Time Frame: Participants will be followed for the duration of their hospital stay expected to be an average of 3-5 days

Those patients receiving blood products. Standardised protocol is as follows:

The criterion for transfusion of blood products will be a haemoglobin < 80g/L or a haemoglobin <100g/L in a patient with ischaemic heart disease or with significant symptomatology
Participants will be followed for the duration of their hospital stay expected to be an average of 3-5 days
Length of Stay (LOS)
Time Frame: Average length of stay is expected to be 3 to 5 days
Day of surgery is counted as Day 0.
Average length of stay is expected to be 3 to 5 days
Range of Passive Flexion
Time Frame: Days 1-3
Range of motion measured in degrees for postoperative days 1 to 3
Days 1-3
Range of Active Flexion
Time Frame: Days 1-3
Range of motion measured in degrees on postoperative days 1-3
Days 1-3
Perioperative Fluid Administration
Time Frame: Day 1
Intravenous fluid (excluding blood transfusion) given during and first 24 hours after surgery
Day 1

Collaborators and Investigators

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

Sponsor

Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS

Investigators

  • Principal Investigator: Jacob T Munro, MBChB, FRACS, Department of Surgery, The University of Auckland

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

December 1, 2014

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

September 18, 2014

First Submitted That Met QC Criteria

October 27, 2014

First Posted (Estimate)

October 29, 2014

Study Record Updates

Last Update Posted (Actual)

May 20, 2020

Last Update Submitted That Met QC Criteria

May 12, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRACKS Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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.

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