Clinical trial NCT06208267: Tranexamic Acid Use on Pain, Mobility and Bleeding Following Total Hip and Total Knee Arthroplasty
Official title: The Impact of Additional Post-operative Doses of Tranexamic Acid on Pain, Mobility and Bleeding Following Total Hip and Total Knee Arthroplasty: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Postoperative Bleeding
Lead sponsor: St. Mary's Research Center, Canada
Sponsor class: OTHER
First posted: 2024-01-17
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tranexamic acid (TXA) is an anti-fibrinolytic agent developed in the 1960s that has been safely used to reduce blood loss, transfusion rates and bleeding-associated mortality in trauma, obstetrics and orthopedic surgery, including hip fracture care and arthroplasty.

The efficacy and safety profile of TXA has been extensively studied in numerous clinical trials and observational studies. Its wide range of applications, combined with its favourable risk-benefit ratio, has led to the incorporation of TXA into clinical guidelines and protocols worldwide.

This RCT aims to compare the current standard dosing for TXA to additional TXA doses given orally post-operatively for THA and TKA patients. The goal is to compare the following between study groups: visible bleeding on post-operative dressing, mobilization (steps, amount of time moving around), pain (visual analog scale), function (Oxford hip and knee scales) and ROM at four to six weeks.

Detailed description: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are some of the most common surgical procedures performed in elderly patients, with the main indication being end-stage osteoarthritis. While these procedures can result in a significant amount of bleeding, pain and stiffness post-operatively, they have been increasingly performed as day surgeries and with reduced length of stay.

Tranexamic acid (TXA) is an anti-fibrinolytic agent developed in the 1960s that has been safely used to reduce blood loss, transfusion rates and bleeding-associated mortality in trauma, obstetrics and orthopedic surgery, including hip fracture care and arthroplasty.

The efficacy and safety profile of TXA has been extensively studied in numerous clinical trials and observational studies. Its wide range of applications, combined with its favourable risk-benefit ratio, has led to the incorporation of TXA into clinical guidelines and protocols worldwide.

The current standard of care at St-Mary's for TXA use is one gram given intravenously (IV) at the beginning of the replacement and one gram given during cementation. However, despite the established benefits of TXA, the optimal dosing regimen continues to be an area of ongoing research and discussion.

TXA and post-operative hemoglobin and hematocrit levels The use of TXA in knee and hip arthroplasty has been shown to have clear and significant benefits in reducing the post-operative drop in hemoglobin (Hb) and hematocrit (Hct) but the duration of use has ranged from a single pre-operative dose to a prolonged 14-day course. Researchers reported higher post-operative Hb and Hct following THA and TKA using a three-day course of TXA compared to a single pre-operative dose of 1.5g. However another study, showed no added benefit of the addition of a second post-operative dose to the single pre-operative dose. Similarly, an randomized controlled trial (RCT) comparing TXA doses at pre, during and three hours post-operative to the same with additional doses at six and 12 hours and showed no added benefit of the additional two doses on Hb or Hct levels. In contrast to this, three RCTs performed in 2019 and 2021 showed improved Hb and Hct levels with TXA use beyond a minimum of seven hours post-operatively and two involved the use of TXA given by mouth (PO), which is ideal in the ambulatory setting.

TXA and Ambulation/Motion The majority of the studies involving varying doses of TXA following THA and TKA have not assessed articular motion nor ambulation post-operatively. These can have an impact on patient satisfaction as well as the ability to mobilize and be able to leave the hospital earlier. TXA was compared to placebo and demonstrated that patients who received TXA ambulated 20% more during physiotherapy sessions. Several TXA regimens with patients receiving a minimum of three post-operative doses (maximum of four post-operative doses were studied),showed having significantly better range of motion (ROM) than patients who received less. Additionally, these patients reported less post-operative pain.

TXA and Complications

No increase in adverse events were reported in any of these studies following prolonged TXA use. Cardiovascular events, deep vein thrombosis (DVT), pulmonary embolism (PE), renal failure or superficial thrombosis were not different among study groups in the rare cases where they occurred, even with oral TXA given for up to 14 days post-operatively

. At St-Mary's Hospital, we perform a large number of TKAs and THAs, around 1100 per year (600 knees, 500 hips), making us the most productive hospital performing these procedures in Québec. Also, partly driven by the constraints of the pandemic over the past three years, we have successfully and safely reduced the length of stay for our patients and converted hundreds of patients to day surgery. Bleeding, however, remains a significant source of patient anxiety, with 10% of our ambulatory cases needing additional CLSC care or even return to hospital. Rapid mobilization and decrease in post- operative pain are also key factors for a rapid and safe discharge from hospital.

In this RCT, we aim to compare our current standard dosing for TXA to additional TXA doses given orally post-operatively for our THA and TKA patients. We will be the first of this type of study to assess patient mobility using a wearable device that will allow for precise measurement of step counts, amount of time moving around and sleep times. Also new compared to previous studies, will be our assessment of bleeding complications requiring intervention and needs for additional hospital or nursing visits, both of which have and impact on the cost of care. Pain (VAS scale), function (Oxford hip and knee scales) and ROM will also be assessed at 4-6 weeks.

Eligibility criteria: Inclusion Criteria:

° All adults undergoing primary TKA and THA at St-Mary's Hospital

Exclusion Criteria:

* Age \< 18 years
* Known hypersensitivity or allergy to TXA
* Previous history of thromboembolic disease
* Active malignancy (all current cancers other than local skin cancer)
* Significant renal disease (hematuria, dialysis, kidney transplant)
* History of convulsions
* Known defective colour vision
* Inability or unwillingness to use MyMobility app
* Unable to communicate in French or English

Primary outcomes:
measure: Step counts at 24 and 48 hours post -operative
timeFrame: Post-operative
Secondary outcomes:
measure: Range of motion (ROM) of the hip (if applicable):
timeFrame: 4 - 6 weeks post op
measure: Range of motion (ROM) of the knee (if applicable):
timeFrame: 4 - 6 weeks post op
measure: Patient self-assessment of functionality and pain measured pre-operatively, 4 to 6 weeks postoperatively, 3 months postoperatively and 6 months post-operatively following total hip arthroplasty utilizing the Oxford Hip Score (OHS):
timeFrame: 4 to 6 weeks postoperatively, 3 months postoperatively and 6 months post-operatively
measure: Patient self-assessment of functionality and pain measured pre-operatively, 4 to 6 weeks postoperatively, 3 months postoperatively and 6 months post-operatively following total knee arthroplasty utilizing the Oxford Knee Score (OKS):
timeFrame: 4 to 6 weeks postoperatively, 3 months postoperatively and 6 months post-operatively
measure: Bleeding Complications requiring intervention
timeFrame: Return to the emergency room or bleeding complications will be noted.
measure: Daily step counts
timeFrame: Post-operative day 0,1,2,3,5,7 and 4 to 6 weeks postoperatively.
measure: Measure of quality of life using the 12-Item Short Form Survey (SF-12):
timeFrame: This measurement will be taken pre-operatively, 4 to 6 weeks postoperatively, 3 months postoperatively and 6 months post-operatively.
measure: Assessment and screening for depression and anxiety in patients utilizing the Hospital Anxiety Depression Scale (HADS) :
timeFrame: Pre-operative
measure: Reported pain self-reported in patient journal and possibly in-patient charts:
timeFrame: These journals and/or in-patient charts will be verified on postoperative day 0,1,2,3,5 and 7.
measure: Assessment of catastrophic thinking related to pain utilizing the Pain Catastrophizing Scale (PCS):
timeFrame: Pre-operative
measure: Reported pain using the visual analog pain (VAS) scale:
timeFrame: This measurement will be collected on postoperative day 0, 1,2,3,5 and 7.
Other outcomes:
Locations:
Study officials:
affiliation: St. Mary's Hospital Centre
name: Jennifer Mutch, MDCM, FRCSC
role: PRINCIPAL_INVESTIGATOR
References: