None listed
Conditions
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.
Interventions
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.
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.
Sponsors
Wesley Medical Research
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Outcome results
None listed