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Trial registered on ANZCTR


Registration number
ACTRN12617000617369
Ethics application status
Approved
Date submitted
27/04/2017
Date registered
1/05/2017
Date last updated
25/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Oral tranexamic acid to reduce blood loss in patients undergoing total knee replacements
Scientific title
Oral tranexamic acid in the reduction of peri-operative blood loss in patients undergoing total knee replacements.
Secondary ID [1] 291760 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Total knee replacement 302985 0
Condition category
Condition code
Surgery 302449 302449 0 0
Other surgery
Blood 302490 302490 0 0
Other blood disorders
Musculoskeletal 302491 302491 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study aims to demonstrate non-inferiority of oral tranexamic acid (TXA) compared to topical and intravenous in reducing blood loss during total knee replacement.
Study: 1g oral TXA 2hr prior to surgery, 1g oral TXA two hours post-surgery and a final 1g oral dose six hours post-surgery.
Patients will receive 2.5mg of oral apixaban twice daily for 15 days, commencing 8 hours post-surgery as prophylactic antithrombotic therapy.
Oral tranexamic acid will be administered under supervision of a health professional (eg nurse) at the times specified. The dose will be supervised to ensure adherence with administration noted on the drug chart. Apixaban adherence will be monitored via return of empty packets by patients.
Intervention code [1] 297872 0
Treatment: Drugs
Comparator / control treatment
Control: 3g topical TXA perioperatively before surgical incision, 1g IV four hours post-surgery and a final 1g oral dose eight hours post-surgery.
Patients will receive 2.5mg of oral apixaban twice daily for 15 days, commencing 8 hours post-surgery as prophylactic antithrombotic therapy.
The first two doses of tranexamic acid will be administered by health professionals and the third oral dose under supervision of a health professional (eg nurse) at the time specified.
This oral dose will be supervised to ensure adherence with administration noted on the drug chart. Apixaban adherence will be monitored via return of empty packets by patients.
Control group
Active

Outcomes
Primary outcome [1] 301862 0
The primary outcome will be blood loss due to surgery.
Timepoint [1] 301862 0
This data will be determined by the amount of blood loss in theatre and the volume collected from the joint drain at ten hours post-surgery.
Secondary outcome [1] 334137 0
Safety will be measured by the incidence of adverse events attributed to TXA, in particular the incidence of DVT.
Timepoint [1] 334137 0
This will be determined by means of Doppler ultrasound at six weeks post-surgery.

Eligibility
Key inclusion criteria
Participants undergoing total knee replacements at John Flynn Hospital
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients currently on anticoagulant therapy, patients with bleeding disorders, patients at high risk of deep vein thrombosis (i.e.Factor V Leiden, past history of deep vein thrombosis)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Quasi-randomisation allocation involving operation theatre allocation
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
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This study aims to have 25 participants in each arm of the study. This was based on 80% power, 95% confidence interval on the average blood loss from total knee replacements of 100-400mL.
Statistical analysis will be performed on GraphPad Instat Version 3 with patient characteristics reported as number and percentage for categorical data, mean+/-standard deviation or median and interquartile ranges for continuous data. Mean data will be used for analysis and comparison using ordinary analysis of variance through non-parametric methods, including Mann-Whitney test for univariate analysis and Dunn’s multiple comparisons test for bivariate analysis. Significance will be defined as* p<0.05, **p<0.01, and ***p<0.001, and graphing performed with GraphPad Prism 6.
.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 7887 0
John Flynn - Gold Coast Private Hospital - Tugun
Recruitment postcode(s) [1] 15841 0
4224 - Tugun

Funding & Sponsors
Funding source category [1] 296261 0
Hospital
Name [1] 296261 0
John Flynn Private Hospital
Address [1] 296261 0
42 Inland Drive Tugun Queensland 4222
Country [1] 296261 0
Australia
Funding source category [2] 296263 0
University
Name [2] 296263 0
Griffith University
Address [2] 296263 0
School of Pharmacy, Griffith University, Gold Coast Campus
58 Parklands Drive Southport Queensland 4215
Country [2] 296263 0
Australia
Primary sponsor type
Hospital
Name
John Flynn Private Hospital
Address
42 Inland Drive Tugun Queensland 4222
Country
Australia
Secondary sponsor category [1] 295178 0
University
Name [1] 295178 0
Griffith University
Address [1] 295178 0
School of Pharmacy, Griffith University, Gold Coast Campus
58 Parklands Drive Southport Queesland 4215
Country [1] 295178 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297497 0
Greenslopes Research and Ethics Commitee
Ethics committee address [1] 297497 0
Greenslopes Private Hospital
Newdegate Street Greenslopes Queensland 4120
Ethics committee country [1] 297497 0
Australia
Date submitted for ethics approval [1] 297497 0
26/04/2017
Approval date [1] 297497 0
06/07/2017
Ethics approval number [1] 297497 0
Protocol 17/25
Ethics committee name [2] 298172 0
Griffith University
Ethics committee address [2] 298172 0
42 Parklands Drive Southport 4222
Ethics committee country [2] 298172 0
Australia
Date submitted for ethics approval [2] 298172 0
06/07/2017
Approval date [2] 298172 0
10/07/2017
Ethics approval number [2] 298172 0
2017/541

Summary
Brief summary
Background and Significance
Evidence supporting the use of tranexamic acid (TXA) in large joint replacements to reduce blood loss and the need for transfusion has been available for many years. To date evidence supports the use of topical or intravenous (IV) TXA, with a recent meta-analysis concluding that the two produced similar effects in the reduction of blood loss due to surgery. Very few studies have investigated the possibility of the use of oral TXA in place of topical/IV. The use of oral TXA has the potential to provide significant financial savings to healthcare facilities, with equivalent quantities of IV TXA ampoules being almost 40-fold more expensive than oral tablets.
Aim and method
This study aims to identify the non-inferiority of oral TXA in the reduction of peri-operative blood loss when compared to a topical/IV regimen in patients undergoing total knee replacements (TKR). In addition, the effect of pre-operative TXA on surgical blood-loss or total blood loss will be examined, in comparison to post-operative. The study will also investigate safety by incidence of deep vein thrombosis (DVT).
The study will comprise of two arms, a study arm which will be treated with and oral TXA regimen and a control arm that will be treated with a currently used topical/IV TXA regimens. The TXA treatment regimens will be as follows:
Study: 1g oral TXA 2hr prior to surgery, 1g oral TXA two hours post-surgery and a final 1g oral dose six hours post-surgery.
Control: 3g topical TXA perioperatively, 1g IV four hours post-surgery and a final 1g oral dose eight hours post-surgery.
Both groups will receive 2.5mg of oral apixaban twice daily for 15 days, commencing 8 hours post-surgery as prophylactic antithrombotic therapy.
All procedures will be conducted by the same orthopaedic surgeon and the anaesthetist for the study arm will remain constant throughout.
The primary outcome will be blood loss due to surgery. This data will be determined by the amount of blood loss in theatre and the volume collected from the joint drain at ten hours post-surgery. Safety will be measured by the incidence of adverse events attributed to TXA, in particular the incidence of DVT. This will be determined by means of Doppler ultrasound at six weeks post-surgery.
Duration and participants
The study will be ongoing with an aim of gathering approximately 50 participants in total, i.e. 25 participants per arm.
All data will be collected from patients undergoing TKRs at John Flynn Private Hospital, all of which will be conducted by the same orthopaedic surgeon. Patients will be excluded if they require adjustments in the TXA regimen or changes to prophylactic antithrombotic therapy. Patient’s will also be excluded if they are undergoing a TKR revision.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74226 0
Mr Liam King
Address 74226 0
Pharmacy Department, Ramsay Health Care
John Flynn Private Hospital
42 Inland Drive Tugun Queensland 4224
Country 74226 0
Australia
Phone 74226 0
+61 7 5598 9155
Fax 74226 0
Email 74226 0
kingliam@ramsayhealth.com.au
Contact person for public queries
Name 74227 0
Mr Liam King
Address 74227 0
John Flynn Private Hospital
42 Inland Drive Tugun Queensland 4224
Country 74227 0
Australia
Phone 74227 0
+61 7 5598 0094
Fax 74227 0
Email 74227 0
kingliam@ramsayhealth.com.au
Contact person for scientific queries
Name 74228 0
Ms Nijole Bernaitis
Address 74228 0
School of Pharmacy, Griffith University, Gold Coast Campus
58 Parklands Drive Southport Queensland 4215
Country 74228 0
Australia
Phone 74228 0
+61 7 5552 9742
Fax 74228 0
Email 74228 0
n.bernaitis@griffith.edu.au

No data has been provided for results reporting
Summary results
Not applicable