Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000582651
Ethics application status
Approved
Date submitted
23/05/2014
Date registered
30/05/2014
Date last updated
1/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of different modes of tranexamic acid administration in patients undergoing total knee arthroplasty.
Scientific title
Effect of intravenous versus intra-articular tranexamic acid on haemoglobin drop and blood loss in patients undergoing total knee arthroplasty - a randomised controlled trial
Secondary ID [1] 284653 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
NIL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
BLOOD LOSS IN TOTAL KNEE ARTHROPLASTY. 291970 0
Condition category
Condition code
Musculoskeletal 292319 292319 0 0
Osteoarthritis
Surgery 292348 292348 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tranexamic acid.
Patients will be assigned to one of 2 treatment groups:
1. Group 1 (Intra-articular TXA group) will receive 100 ml of Saline intravenously, 5 minutes before incision, 3000mg (30ml) of TXA injected in to the knee joint after wound closure and two doses of 100 ml of Saline intra-venously at 8 hourly intervals post-operatively.
2. Group 2 (Intravenous TXA group) will receive 1000mg of TXA in 100ml Saline intravenously 5 minutes before incision and 30ml of Saline injected in to the knee joint after wound closure to make the group comparative with Group 1 and also provide a tamponade effect. Another 1000mg dose of TXA (in 100ml Normal Saline over 15 minutes) will be repeated at 8 hourly intervals post-operatively for another two doses.

Patients undergoing primary total knee arthroplasty will be invited to take part in the study and informed written consent will be obtained from willing participants. Patients undergoing bilateral TKA, those with history of thromboembolic events (deep vein thrombosis, pulmonary embolism or cerebrovascular accident), renal dysfunction (plasma Creatinine level >130 mmol/L) or coagulopathy (INR > 1.4) will be excluded. Also patients with pre-operative anemia (Hb < 120 for females and Hb < 130 for males) will be excluded.
Intervention code [1] 289435 0
Prevention
Intervention code [2] 289452 0
Treatment: Drugs
Comparator / control treatment
Intravenous (IV) Tranexamic acid - Comparator

Control is saline and would be given as detailed in Description of Intervention/exposure section.
Control used is intravenous saline for Group 1, and Intra-articular saline for Group 2.
Control group
Placebo

Outcomes
Primary outcome [1] 292182 0
Reduction in the haemoglobin drop as measured by the difference in the pre-operative and post-operative haemoglobin levels
.
Timepoint [1] 292182 0
day 2 after intervention commencement
Secondary outcome [1] 308382 0
the number of units of blood transfused.
Timepoint [1] 308382 0
within 6 weeks after intervention commencement.
Secondary outcome [2] 308383 0
Transfusion requirements in terms of numbers of patients requiring transfusion
Timepoint [2] 308383 0
within 6 weeks after intervention commencement.
Secondary outcome [3] 308384 0
knee joint swelling as indicated by the circumference of thigh at the level of superior border of patella
Timepoint [3] 308384 0
3 days after intervention commencement.
Secondary outcome [4] 308385 0
pain assessment using visual analogue score.
Timepoint [4] 308385 0
daily for 5 days from intervention commencement.
Secondary outcome [5] 308386 0
passive knee range of motion by using a gonimeter
Timepoint [5] 308386 0
day 3, 2 weeks, 8 weeks.
Secondary outcome [6] 308387 0
infection rates.
Timepoint [6] 308387 0
within 6 weeks after intervention commencement.
Secondary outcome [7] 308388 0
thromboembolic adverse events.
Timepoint [7] 308388 0
within 6 weeks after intervention commencement.

Eligibility
Key inclusion criteria
1. All the patients undergoing total knee arthroplasty under the principal investigators.
2. Able to give consent for the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inflammatory arthropathy.
2. Patients currently on warfarin (Coumadin)
3.Patients on antiplatelet therapy (excluding aspirin)
4.Bleeding diathesis
5.Haematological dysfunction/Abnormal coagulation studies
6. Patients requiring lateral release, synovectomy, or removal of existing hardware during their procedure
7. Renal or liver disease
8. Previous thromboembolic disease
9. Disturbance of colour vision
10.Stroke
11. Pre-operative anemia (Hb < 120 for females and Hb < 130 for males).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer.

The operating team, patients and data collection team will be blinded to the group to which the patients have been randomized. Only the anaesthesiologist who will prepare the treatment solution will be aware of the allocation and will not be involved in data collection or analysis. Post-operatively only the administering nurse will know the drug being administered. Patients and the operative and data collection team will be blinded.
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 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This trial is designed as non-inferiority trial to show that intra-articular tranexamic acid (TXA) is not inferior to intravenous TXA in its effect on the pre-operative post-operative haemoglobin difference. The standard deviation in the pre-post haemoglobin difference from previous published trials was consistently less than 1.1, therefore we have conservatively assumed a standard deviation of 1.1 for our sample size calculation. Our margin of non-inferiority is 0.5g/dL, based on various literature studies. A sample size of 83 participants per group (166 in total) is required for a non-inferiority trial with power of 90%, significance level of 5%.
An intention-to-treat analysis will be used to compare the study groups. A supplementary as-treated analysis will also be used. Both the groups will be statistically analysed for homogeneity and ANOVA will be used for continuous variables, Chi square test for categorical variables.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/06/2014
Actual
16/07/2014
Date of last participant enrolment
Anticipated
31/12/2014
Actual
16/12/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
166
Accrual to date
Final
183
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2492 0
St George Private Hospital - Kogarah
Recruitment postcode(s) [1] 8136 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 289278 0
Self funded/Unfunded
Name [1] 289278 0
SAMUEL J MACDESSI
Country [1] 289278 0
Australia
Primary sponsor type
Individual
Name
SAMUEL J MACDESSI
Address
SYDNEY KNEE SPECIALISTS ,8/19,
KENSINGTON STREET, KOGARAH ,NSW ,2217
Country
Australia
Secondary sponsor category [1] 287951 0
Individual
Name [1] 287951 0
DARREN CHEN
Address [1] 287951 0
SYDNEY KNEE SPECIALISTS ,8/19,
KENSINGTON STREET, KOGARAH ,NSW ,2217
Country [1] 287951 0
Australia
Secondary sponsor category [2] 287952 0
Individual
Name [2] 287952 0
Dr Neville Rowden
Address [2] 287952 0
St George Knee Clinic, 2nd Floor Kirk Place, 15 Kensington Street,, KOGARAH ,NSW ,2217
Country [2] 287952 0
Australia
Secondary sponsor category [3] 287953 0
Individual
Name [3] 287953 0
Dr George Kirsh
Address [3] 287953 0
St George Private Hospital, 1 South Street , Kogarah, NSW,2217
Country [3] 287953 0
Australia
Other collaborator category [1] 277971 0
Individual
Name [1] 277971 0
Ian Harris
Address [1] 277971 0
Whitlam Orthopaedic Research Centre
Ingham Institute for Applied Medical Research
1 Campbell St
Liverpool, NSW 2170
Country [1] 277971 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291047 0
Hunter New England Research Ethics & Governance Unit
Ethics committee address [1] 291047 0
Ethics committee country [1] 291047 0
Australia
Date submitted for ethics approval [1] 291047 0
25/09/2013
Approval date [1] 291047 0
10/06/2014
Ethics approval number [1] 291047 0
14/04/09/3.06

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48642 0
Dr Samuel J Macdessi
Address 48642 0
Sydney Knee Specialists. Suite 8, 19 Kensington Street. Kogarah NSW 2217
Country 48642 0
Australia
Phone 48642 0
+ 61 2 8307 0333
Fax 48642 0
+ 61 2 8307 0334
Email 48642 0
[email protected]
Contact person for public queries
Name 48643 0
Samuel J Macdessi
Address 48643 0
Sydney Knee Specialists. Suite 8, 19 Kensington Street. Kogarah NSW 2217
Country 48643 0
Australia
Phone 48643 0
+ 61 2 8307 0333
Fax 48643 0
+ 61 2 8307 0334
Email 48643 0
[email protected]
Contact person for scientific queries
Name 48644 0
Samuel J Macdessi
Address 48644 0
Sydney Knee Specialists. Suite 8, 19 Kensington Street. Kogarah NSW 2217
Country 48644 0
Australia
Phone 48644 0
+ 61 2 8307 0333
Fax 48644 0
+ 61 2 8307 0334
Email 48644 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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