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Trial registered on ANZCTR


Registration number
ACTRN12616000723482
Ethics application status
Approved
Date submitted
27/05/2016
Date registered
1/06/2016
Date last updated
28/11/2018
Date data sharing statement initially provided
28/11/2018
Date results information initially provided
28/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Intravenous tranexamic acid ("TXA") and its effect on operating conditions, blood loss, post-operative pain and complications in patients undergoing total shoulder replacement.
Scientific title
Effect of systemic tranexamic acid use on operating conditions, blood loss, post-operative pain and complications in patients undergoing shoulder arthroplasty.
Secondary ID [1] 289324 0
None
Universal Trial Number (UTN)
U1111-1183-3447
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Blood loss in total shoulder arthroplasty 298920 0
Condition category
Condition code
Musculoskeletal 298998 298998 0 0
Osteoarthritis
Surgery 298999 298999 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1 (TXA group) will receive 2000mg (20ml) of Tranexamic Acid (TXA) intravenously 5 minutes before incision.
Intervention code [1] 294880 0
Treatment: Drugs
Comparator / control treatment
Group 2 (Control group) will receive 2000mg (20ml) of Saline intravenously 5 minutes before incision..
Control group
Placebo

Outcomes
Primary outcome [1] 298471 0
Change in haemaglobin level as measured by the difference between pre-operative and post-operative levels as assessed by serum assay.
Timepoint [1] 298471 0
Pre-operative haemaglobin will be assessed the day before operation. Post-operative haemaglobin will be assessed in the morning of the first day after operation.
Primary outcome [2] 298485 0
Change in haemocrit as measured by the difference between pre-operative and post-operative levels as assessed by serum assay.
Timepoint [2] 298485 0
Pre-operative haemocrit will be assessed the day before operation. Post-operative haemocrit will be assessed in the morning of the first day after operation.
Secondary outcome [1] 324233 0
Operative time defined as time from induction of anaesthesia until wound closure as timed by surgical assistant with stopwatch.
Timepoint [1] 324233 0
Operative time will be calculated at the conclusion of the operation (day 0).
Secondary outcome [2] 324234 0
Transfusion requirement as measured by data linkage to patient medical records.
Timepoint [2] 324234 0
Within 6 weeks after intervention commencement.
Secondary outcome [3] 324235 0
Pain assessment using visual analogue score.
Timepoint [3] 324235 0
Measured daily for 5 days starting from 24 hours after operation.
Secondary outcome [4] 324236 0
Passive shoulder range of motion by using a goniometer.
Timepoint [4] 324236 0
Day 3, 2 weeks and 8 weeks post operation.
Secondary outcome [5] 324237 0
Infection rates as measured by data linkage to patient medical records.
Timepoint [5] 324237 0
Within 6 weeks after intervention commencement.
Secondary outcome [6] 324238 0
Thromboembolic adverse events as measured by data linkage to patient medical records.
Timepoint [6] 324238 0
Within 6 weeks after intervention commencement.
Secondary outcome [7] 324294 0
Procedure complexity rating as measured by the operating surgeon selecting either "more complex than usual", "as usual" or "less complex than usual" on a checklist.
Timepoint [7] 324294 0
At the conclusion of the operation.
Secondary outcome [8] 324295 0
Operative field visibility rating as measured by the operating surgeon selecting either "excellent", "good", "fair"or "poor" on a checklist.
Timepoint [8] 324295 0
At the conclusion of the operation.
Secondary outcome [9] 324296 0
Drain output measured in cc.
Timepoint [9] 324296 0
8 hours post operation, 16 hours post operation and 24 hours post operation.
Secondary outcome [10] 324297 0
Post-operative haematoma occurrence as measured by data linkage to patient medical records.
Timepoint [10] 324297 0
Within 24 hours post operation.
Secondary outcome [11] 324298 0
Time spent in recovery room as measured by the difference between time of arrival to time of departure.
Timepoint [11] 324298 0
Time of departure from recovery room.
Secondary outcome [12] 324299 0
Time spent in hospital as measured by the difference between date of admission to date of discharge.
Timepoint [12] 324299 0
Date of discharge.

Eligibility
Key inclusion criteria
1. Patients who have consented for anatomic or reverse shoulder arthroplasty under one of the principal investigators.
2. Patients who are capable of and have given informed consent for their participation in this study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients allergic to tranexamic acid
2. Patients with a failed arthroplasty requiring revision
3. Patients with history of deep venous thrombosis or pulmonary embolism
4. Patients with cardiovascular disease, including coronary disease or peripheral arteriopathy
5. Patients with renal or liver failure
6. Patients with a known coagulopathy
7. Patients that refuse a potential transfusion

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)
Central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
None.
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size was calculated based on the primary objective. It was decided to replicate work done by Gillespie et al (2015) who found an average change in haemaglobin level of 2.6g/dL in the placebo group and 1.7g/dL in the TXA group (p < .001) with 111 patients. It was decided that increasing the subjects from 111 to 150 patients might improve the power of the study.

Correlation analysis, including univariate and multivariate analyses will be used to determine the correlation between systemic administration of TXA and the selected outcome criteria. Subgroup analysis will be carried between the different types of prosthesis (reverse versus anatomic). P value <0.5 will be considered as statistically significant. All data will be entered into Socrates Orthopaedic Outcomes Software (Ortholink Pty Ltd, Sydney, Australia).

Recruitment
Recruitment status
Completed
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)
NSW
Recruitment hospital [1] 5861 0
North Shore Private Hospital - St Leonards
Recruitment hospital [2] 5862 0
Mater Sydney - North Sydney
Recruitment hospital [3] 6783 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 13302 0
2065 - St Leonards
Recruitment postcode(s) [2] 13309 0
2060 - North Sydney
Recruitment postcode(s) [3] 14439 0
2065 - Royal North Shore Hospital

Funding & Sponsors
Funding source category [1] 293697 0
Other Collaborative groups
Name [1] 293697 0
Sydney Shoulder Research Institute
Address [1] 293697 0
Suite 201
Level 2
156 Pacific Highway
St Leonards NSW 2065
Country [1] 293697 0
Australia
Primary sponsor type
Individual
Name
Dr Benjamin Cass
Address
Sydney Shoulder Research Institute
Suite 201
Level 2
156 Pacific Highway
St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 292531 0
None
Name [1] 292531 0
Address [1] 292531 0
Country [1] 292531 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295137 0
North Shore Private Hospital Ethics Committee
Ethics committee address [1] 295137 0
North Shore Private Hospital
Westbourne Street
St Leonards NSW 2065
Ethics committee country [1] 295137 0
Australia
Date submitted for ethics approval [1] 295137 0
11/04/2016
Approval date [1] 295137 0
25/10/2016
Ethics approval number [1] 295137 0
Ethics committee name [2] 295138 0
St Vincent's Hospital Sydney Human Research Ethics Committee
Ethics committee address [2] 295138 0
Research Office
Level 6, de Lacy Building
St Vincent's Hospital
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [2] 295138 0
Australia
Date submitted for ethics approval [2] 295138 0
11/05/2016
Approval date [2] 295138 0
13/09/2016
Ethics approval number [2] 295138 0

Summary
Brief summary
This was a multicentre multisurgeon prospective doubleblinded randomized and controlled trial looking at the effectiveness of single dose intravenous administration of Tranexamic Acid (TXA) in patients undergoing shoulder arthroplasty.

The aim of this study was to extend Level I category evidence of the known benefits of TXA to shoulder arthroplasty. The primary objective of this study was to test the hypothesis that systemic use of Tranexamic acid improves operating conditions, decreases blood loss, postoperative pain and complications such as haematoma and need for transfusion. The secondary objective was to carry out subgroup analysis between reverse and anatomical shoulder arthroplasty with the hypothesis that reverse causes more blood loss than anatomic.

All consecutive patients presenting to an elective orthopaedic consultation with a failed nonoperative management of shoulder arthritis indicated for shoulder arthroplasty were considered eligible for this study. After having been screened for inclusion and exclusion criteria, read the information sheet and signed the consent form, patients were blindly randomized to one of 2 groups: Systemic TXA or Control.

Patients’ general demographic characteristics such as age, sex, dominance, diagnosis, BMI, American Society of Anaesthesia (ASA) score and other relevant comorbidities were collected in a deidentified database locked on a password-protected computer.

During the surgery, patients were administered either 2mg of intravenous TXA or a placebo equivalent (saline solution). Analysed outcome variables included: surgeon’s rating of surgical field visibility and overall appreciation of the complexity of the procedure, operative time, pre- and postoperative haemoglobin and haematocrit levels, drain output at 6,12 and 24 hours, need for transfusion, occurrence of postoperative haematoma, postoperative pain Visual Analog Scale (pVAS), time spent in recovery room and hospital room.
Trial website
http://www.ssri.net.au/research/txa-study/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66246 0
Dr Benjamin Cass
Address 66246 0
Sydney Shoulder Research Institute
Suite 201, Level 2
156 Pacific Highway
St Leonards NSW 2065
Country 66246 0
Australia
Phone 66246 0
+61 2 9460 8888
Fax 66246 0
+61 2 9460 6064
Email 66246 0
cassadmin@sydneyshoulder.com.au
Contact person for public queries
Name 66247 0
Miss Jasmin Gwynne
Address 66247 0
Sydney Shoulder Research Institute
Suite 201, Level 2
156 Pacific Highway
St Leonards NSW 2065
Country 66247 0
Australia
Phone 66247 0
+61 2 9460 8813
Fax 66247 0
+61 2 9460 6064
Email 66247 0
jasmin@sydneyshoulder.com.au
Contact person for scientific queries
Name 66248 0
Dr Benjamin Cass
Address 66248 0
Sydney Shoulder Research Institute
Suite 201, Level 2
156 Pacific Highway
St Leonards NSW 2065
Country 66248 0
Australia
Phone 66248 0
+61 2 9460 8888
Fax 66248 0
+61 2 9460 6064
Email 66248 0
cassadmin@sydneyshoulder.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Now that analysis has been completed, all study data has been deidentified, stored confidentially and will not be used for any further research unless further ethics approval is granted.

What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – plain English summary
Our results show that a single dose of tranexamic acid (TXA) administered intravenously at the start of shoulder replacement surgery (arthroplasty) decreases blood loss and drain tube output regardless of the type of implant used (i.e. anatomic aka “total” or reverse). Patients who received TXA had lower drain outputs at all time points: 41ml vs 133ml at 8 hours, 75ml vs 179ml at 16 hours and 94ml vs 226ml at 24 hours. They also had higher postoperative Haemaglobin (Hb) (12.3 vs 11.4), lower change in Hb (1.7 vs 2.3), lower total Hb loss (0.078g vs 0.103g), lower blood volume loss (0.55L vs 0.74L), higher postoperative Haematocrit (36.7 vs 34.6) and lower Haematocrit change (5.4 vs 7.6). We found no difference in pain scores between the group that received TXA and the group that received Placebo. We also found no difference on the other measured outcomes (field visibility, operation complexity or time, time spent in the recovery bay or time spent in hospital overall).