ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619000339156

Ethics application status

Approved

Date submitted

15/02/2019

Date registered

5/03/2019

Date last updated

6/12/2019

Date data sharing statement initially provided

5/03/2019

Type of registration

Retrospectively registered

Titles & IDs

Public title

Optimisation of the use of tranexamic acid, a medication used to treat or prevent excessive blood loss during total knee replacement surgery

Scientific title

A prospective, randomised non-blinded pilot study to optimise oral tranexamic acid dosing in primary total knee arthroplasty

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

osteoarthritis

total knee arthroplasty

Condition category

Condition code

Musculoskeletal

Osteoarthritis

Surgery

Other surgery

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The dosage and frequency of dosing of tranexamic acid for each participant will be determined by a personalised dosing algorithm developed specifically for this study. A Shiny application calculator based on a published population pharmacokinetic model (Lanoiselee, J., et al., Is tranexamic acid exposure related to blood loss in hip arthroplasty? A pharmacokinetic-pharmacodynamic study. Br J Clin Pharmacol, 2018. 84(2): p. 310-319.) and pharmacokinetic information for oral TXA (Pilbrant, A., M. Schannong, and J. Vessman, Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol, 1981. 20(1): p. 65-72.), has been developed to display the median expected concentration-time profile after dosing of oral TXA. Participant characteristics, such as total body weight, sex, age, serum creatinine are variables that affect the PK of TXA and can be specifically set in the Shiny application for each individual participant. This will then tailor the median expected concentration-time profile after dosing of oral TXA towards the entered participant characteristics. Different dosing intervals and the number of days of treatment to which a participant would be randomised as part of the study can also be set by a user of the application. The tranexamic acid comes in the form of a 500 mg tablet which will be titrated and prescribed to the participant in line with the algorithm result.
Group 1 – Participants will receive an individualised oral dose of tranexamic acid one hour prior to total knee replacement surgery
Group 2 – Participants will receive an individualised oral dose of tranexamic acid one hour prior to surgery and continue individualised tranexamic acid to maintain therapeutic plasma tranexamic acid levels (10 – 50 mg/L) for 24 hours following total knee replacement surgery.
Group 3 - Participants will receive an individualised oral dose of tranexamic acid one hour prior to surgery and continue individualised tranexamic to maintain therapeutic plasma tranexamic levels (10 – 50 mg/L) for 72 hours following total knee replacement surgery.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Dose comparison

Control group

Dose comparison

Outcomes

Primary outcome [1]

Time to consistently achieve 90 degrees of knee flexion. Range of motion/flexion will be measured using a double-armed goniometer by the number of degrees from the starting position of the knee joint to its position at the end of its full range of the movement.

Timepoint [1]

The change in range of motion measured daily from pre-surgery (day 0) to day 4 post-surgery will be recorded as a percentage change. The post-operative day on which the participant achieves 90 degrees of knee flexion will be recorded. If the participant is discharged prior to achieving 90 degrees flexion, the participant will be followed up via telephone. These participants will be assessed by an outpatient physiotherapist until 90 degrees flexion is documented.

Primary outcome [2]

Maximum change in knee girth in cm as a percentage increase. Participants will have leg girth measured (at mid-patellar level) before surgery and once the bandages have been removed using a paper tape measure whilst in lying position.

Timepoint [2]

Measurements will be on admission and in the morning of days 1, 2, 3 and 4 post-operatively.

Primary outcome [3]

Quality of life measured using Oxford Knee Score

Timepoint [3]

Participants will be complete the assessment in writing pre-operatively and over the telephone at 6 weeks and 6 months post-operatively.

Secondary outcome [1]

Blood loss as assessed by blood sample assay for haemoglobin

Timepoint [1]

Calculated as difference between admission haemoglobin (Hb) and lowest post-operative Hb during hospital stay or prior to blood transfusion.

Secondary outcome [2]

Pain (using verbal pain score)

Timepoint [2]

Measured each day whilst in hospital prior to discharge

Eligibility

Key inclusion criteria

- participants of either sex scheduled to undergo a primary, unilateral TKA (either anterior or posterior approach, but not joint resurfacing)
- available for follow up at 6 months post-surgery
- willingness to provide written, informed consent
- willingness to comply with the study

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- known allergy to TXA
- acquired disturbances to colour vision
- preoperative use of anticoagulants (within 5 days of surgery)
- fibrinolytic disorders requiring intraoperative fibrinolytics
- coagulopathy, history of arteriolar or venous thromboembolic disease
- pregnancy or breastfeeding
- hepatic failure
- haemoglobin <10g/dL

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Not Applicable

Type of endpoint/s

Statistical methods / analysis

The primary outcomes are time to consistently achieve 90 degrees flexion and the maximal change in knee girth as a percentage increase. Secondary outcomes include blood loss (defined as the difference between the pre-operative Hb and the lowest Hb, be that the day 4 Hb or the Hb prior to transfusion), daily pain scores and change in Oxford Knee Score. The comparisons of interest are between group 1 and group 2, group 1 and group 3 and group 2 and group 3. Categorical variables will be examined using a Pearson Chi-squared test or Fisher’s Exact test. Continuous variables will be examined using a one-way anova or Kruskal-Wallis test. A p-value <0.05 will be considered statistically significant.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

Actual

19/07/2018

Date of last participant enrolment

Anticipated

Actual

18/02/2019

Date of last data collection

Anticipated

19/08/2019

Actual

20/11/2019

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

The Wesley Hospital - Auchenflower

Recruitment postcode(s) [1]

4066 - Auchenflower

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Wesley Medical Research

Address [1]

Level 8, The Wesley Hospital, 451 Coronation Drive, Auchenflower, Queensland, 4066

Country [1]

Australia

Primary sponsor type

Charities/Societies/Foundations

Name

Wesley Medical Research

Address

Level 8, The Wesley Hospital, 451 Coronation Drive, Auchenflower, Queensland, 4066

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

UnitingCare Health Human Research Ethics Committee

Ethics committee address [1]

The Wesley Hospital
PO Box 499
Auchenflower Qld 4066

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

19/05/2017

Ethics approval number [1]

1714

Summary

Brief summary

Total knee replacement (TKR) is a major surgical operation that will be conducted in increasing numbers in Australia over the next 10 years. The patient’s post-operative course is typically painful and can have significant associated morbidity. The recovery process is also expensive due to the intensive nursing and physiotherapy that are required for rehabilitation. Optimising and streamlining this clinical pathway is vital for improved patient outcomes and the overall health budget. 

Whilst there is evidence to support the early mobilisation of patients post TKR (to reduce venous thromboembolism (VTE)), respiratory complications and bowel dysfunction), this may cause bleeding in and around the joint. This blood creates swelling, pain, reduced mobility, decreased knee flexion and an increased potential for infection. The primary goal of this study is to decrease surgical site bleeding as the patient mobilises in the early post-operative period. We aim to assess this by a number of clinical outcome measures. 

The study will use oral tranexamic acid (TXA) to reduce post-operative bleeding. It is already accepted that TXA is effective in reducing blood loss for TKR, whether it is used in the intravenous, topical or oral route. Current literature shows that there have been no attempts in individualising oral dosing of TXA for a patient, based on their weight and renal function. Additionally, evidence is sparse regards to identifying the benefits of achieving acceptable therapeutic target TXA exposure in plasma over a longer period while the potential for bleeding at the surgical site to occur is still high. We aim to show that therapeutic exposure of TXA can be used safely over a prolonged period and that this will improve outcomes.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Sue Clark

Address

Wesley Anaesthesia and Pain Management
Suite 17, level 2
Wesley Medical Centre
17/40 Chasely St
AUCHENFLOWER QLD 4066

Country

Australia

Phone

+61 7 3377 0500

Fax

susieclark@me.com

Contact person for public queries

Name

Kelley Foster

Address

Wesley Medical Research, Level 8, The Wesley Hospital, 451 Coronation Drive, Auchenflower, Queensland 4066

Country

Australia

Phone

+61737211503

Fax

kfoster@wesleyresearch.com.au

Contact person for scientific queries

Name

Kelley Foster

Address

Wesley Medical Research, Level 8, The Wesley Hospital, 451 Coronation Drive, Auchenflower, Queensland 4066

Country

Australia

Phone

+61737211503

Fax

kfoster@wesleyresearch.com.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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