Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000670178
Ethics application status
Approved
Date submitted
6/04/2019
Date registered
6/05/2019
Date last updated
23/06/2021
Date data sharing statement initially provided
6/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Are we giving appropriate dose of tranexamic acid in hip replacement surgery?
Scientific title
Pharmacokinetics of tranexamic acid in adult patients undergoing elective hip replacements: an in-vivo study.
Secondary ID [1] 297894 0
Nil
Universal Trial Number (UTN)
U1111-1231-2199
Trial acronym
ORACLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Joint replacement surgery 312274 0
Condition category
Condition code
Anaesthesiology 310823 310823 0 0
Other anaesthesiology

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Intravenous tranexamic acid 15 mg/kg is administered as a routine practice during hip replacement surgery.24 adult patients 18 years and over, undergoing elective unilateral primary hip replacements and 10 patients undergoing elective revision hip replacements under general anaesthesia, and receiving intravenous tranexamic acid 15 mg/kg at The Prince Charles Hospital will be enrolled. Additional intravenous tranexamic acid may be administered according to the discretion of surgeon. No topical tranexamic acid will be administered. Blood samples will be collected at the time points: baseline, 5 minutes after tranexamic acid, skin incision, skin closure, 3 hours, 8 hours and 24 hours after tranexamic acid, for assessing tranexamic acid levels and to measure biomarkers to describe changes to the extent of fibrinolysis during surgery. This will involve additional blood samples at these time points. If there is existing cannula, blood samples will be drawn from them. Participants will be observed from induction of anaesthesia until 24 hours following surgery. A population pharmacokinetic-pharmacodynamic model will be developed on the concentration-time data generated and fibrinolysis biomarkers, using the software PMetrics, from which dosing simulations will be performed and recommendations for effective dosing of tranexamic acid will be obtained.
Intervention code [1] 314121 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319662 0
Plasma concentration of tranexamic acid at various time points.
Timepoint [1] 319662 0
at baseline, post tranexamic acid administration - at 5 minutes, skin incision, skin closure, 3 hours, 8 hours
Primary outcome [2] 319673 0
Tranexamic acid exposure time, when plasma concentration of tranexamic acid is above the minimum threshold.
Timepoint [2] 319673 0
until 8 hours post tranexamic acid administration
Secondary outcome [1] 369130 0
Degree of fibrinolysis

This will be assessed using ROTEM, PAP complex levels, clot lysis assays, D-dimer levels.
Timepoint [1] 369130 0
baseline, post Tranexamic acid administration: skin incision, skin closure, 8 hours, 24 hours.
Secondary outcome [2] 369131 0
total number of blood and blood products transfused until discharge, as per the information obtained from the blood bank
Timepoint [2] 369131 0
All these outcomes will be collected before surgery and at discharge
Secondary outcome [3] 369711 0
Difference between baseline and lowest postoperative haemoglobin, as assessed by laboratory testing of blood samples. These are routinely done for orthopaedic patients as a standard of care.
Timepoint [3] 369711 0
Presurgery and at discharge
Secondary outcome [4] 369712 0
Length of hospital stay as documented in medical records
Timepoint [4] 369712 0
at discharge
Secondary outcome [5] 369713 0
Major clinical adverse events as documented in the records by the parent team.These include mortality and major morbidity including thrombotic complications, wound infection, bleeding and other adverse outcomes
Timepoint [5] 369713 0
data will be collected at discharge
Secondary outcome [6] 369714 0
Anaemia as calculated from the haemoglobin results.
Timepoint [6] 369714 0
baseline and at discharge
Secondary outcome [7] 369715 0
Estimated blood loss with Gross formula ( Gross et al, Anaesthesiology, 1983)

Estimated blood volume multiplied by the ratio between the initial haematocrit- final haematocrit/ average of initial and minimum haematocrit.

Estimated blood volume using Nadler's formula ( Nadler et al, Surgery, 1962)
Timepoint [7] 369715 0
3 days following surgery

Eligibility
Key inclusion criteria
Patient undergoing unilateral total hip replacment and receiving tranexamic acid; Age greater than or equal to 18 years old; Written informed consent obtained from the patient
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Consent not obtained; Patients in whom tranexamic acid would be contraindicated such as cerebrovascular or coronary event in the past 12 months, end stage renal disease, those at a very high risk of thromboembolism, or documented allergy etc; Patients with communication barrier due to language issues; Urgent arthroplasty or hemiarthroplasty due to hip fractures; Bilateral THR

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We aim to enrol 24 patients undergoing primary total hip replacements, 10 patients undergoing revision THR and receiving tranexamic acid. The pharmacokinetics of TXA and the ability to achieve pharmacodynamic target of the concentration to achieve fibrinolysis will be determined using a population pharmacokinetic-pharmacodynamic modelling approach using using PMetrics 1.5.0 with RStudio 0.99.902 and digital compiler Gfortran 5.2. Additionally, the pharmacokinetic-pharmacodynamic model will aim to determine if significant correlations exist between demographic and clinical factors on the pharmacokinetics of TXA. If one or more of the variables are found to have a significant effect on the pharmacokinetics of the drug, then it can be incorporated into the final pharmacokinetic model. Other statistical analyses to test the secondary aims will be tested with Mann-Whitney U tests or Students t-test where appropriate using the statistical package, SPSS (version 17.0, Illinois, USA).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/07/2021
Actual
Date of last participant enrolment
Anticipated
31/08/2021
Actual
Date of last data collection
Anticipated
1/10/2021
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13568 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 26214 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 302423 0
Government body
Name [1] 302423 0
Metro North Hospital and Health Service Collaborative research grant 2020
Country [1] 302423 0
Australia
Primary sponsor type
Individual
Name
Usha Gurunathan
Address
Department of Anaesthesia, The Prince charles Hospital, Rode Road, Chermside , Queensland - 4032
Country
Australia
Secondary sponsor category [1] 302323 0
None
Name [1] 302323 0
None
Address [1] 302323 0
Country [1] 302323 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303084 0
The Prince Charles Hospital Human Research Ethics committee
Ethics committee address [1] 303084 0
The Prince Charles Hospital Research and Ethics, Rode Road, Chermside, Queensland- 4032
Ethics committee country [1] 303084 0
Australia
Date submitted for ethics approval [1] 303084 0
31/01/2020
Approval date [1] 303084 0
19/05/2020
Ethics approval number [1] 303084 0

Summary
Brief summary
According to the annual report from national joint replacement registry, around 32000 primary total hip replacements (THR) have been performed in 2017 in Australia. Reported prevalence of blood transfusion in THR is around 24%. Blood transfusions are associated with infectious risk and complications such as acute lung injury, and acute or delayed immune responses. Tranexamic acid (TXA) has been widely used for its anti- fibrinolytic effect in major joint replacement surgery. It has been shown to prevent excess bleeding and reduce the risk of blood transfusion following lower limb joint replacements. Current dosing of TXA for joint replacement surgery is not based on rigorous scientific evidence and dosing based on bleeding endpoints may be sub-optimal. In this study, we propose investigating the use of biomarkers to describe the extent of fibrinolysis as dosing endpoints for the physiological effect of TXA. From this, we will provide recommendations for effective dosing regimens of TXA in patients undergoing THR.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92414 0
Dr Usha Gurunathan
Address 92414 0
Department of Anaesthesia, The Prince Charles Hospital, Rode Road, Chermside, Queensland - 4032
Country 92414 0
Australia
Phone 92414 0
+61 7 3139 4000
Fax 92414 0
Email 92414 0
[email protected]
Contact person for public queries
Name 92415 0
Dr Usha Gurunathan
Address 92415 0
Department of Anaesthesia, The Prince Charles Hospital, Rode Road, Chermside, Queensland - 4032
Country 92415 0
Australia
Phone 92415 0
+61 7 3139 4000
Fax 92415 0
Email 92415 0
[email protected]
Contact person for scientific queries
Name 92416 0
Dr Usha Gurunathan
Address 92416 0
Department of Anaesthesia, The Prince Charles Hospital, Rode Road, Chermside, Queensland - 4032
Country 92416 0
Australia
Phone 92416 0
+61 7 3139 4000
Fax 92416 0
Email 92416 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data is not useful to the public


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.