Tranexamic Acid Dosing for Major Joint Replacement Surgery (TXA-Dosing)

Over 1.7 million hip and knee replacements are performed every year worldwide. These surgeries are associated with high blood loss and transfusion rates. In older patients, the high blood loss can result in postoperative anemia. Anemia is a condition where there is a lack of healthy red blood cells to carry oxygen around the body. This means, the patient may need a blood transfusion. This can result in different immune responses such as lung injury, fluid overload, and sepsis.

The purpose of this study is to find an optimal dose of tranexamic acid (TXA) to be given during a hip or knee replacement surgery. TXA is one of the drugs given during surgery because it lowers the amount of bleeding and the risk of a blood transfusion.

Individuals who are chosen to participate in the study will be split into two separate groups. After anesthesia is administered, study participant will be given the hospitals standard dose of TXA which is 20mg/kg. However, in patients with kidney problems and lower kidney functions, the dose will be lowered because TXA is filtered out of the body through the kidneys. Throughout the surgery and after it, patients will have about 30-50mL (3-5 tablespoons) of blood samples drawn at specific time points. This will be done through IV line which will stay in place during the surgery and post operation to minimize the amount of needle puncturing's.

This study will help to development a new dosing guideline for TXA in patients who are undergoing joint replacement surgery.

Study Overview

• Status: Completed
• Conditions: Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip
• Intervention / Treatment: Drug: Tranexamic acid

Detailed Description

Our study follows a prospective cohort study design without randomization or blinding. 20 patients undergoing unilateral hip or knee replacement will be recruited and stratified into 2 groups (each with 10 patients) with either glomerular filtration rate (GFR) < 60 mL/min/1.73m2 (and dialysis) or GFR ≥ 60 mL/min/1.73m2. This GFR cut-off was chosen based on previous data showing low variability at GFR below and above 60, and plasma TXA levels differed due to reduction in TXA clearance rates between patients in each group.

After spinal/regional or general anesthesia, a single intravenous bolus of 20 mg/kg TXA will be administered (as per our standard of care) over 15 minutes. Serial 4-5 ml blood samples will be drawn at: baseline/pre-TXA administration, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 6h+/-2h and 12h+/-4h post-bolus. These time points capture 2-3 TXA half-lives, including peak and end of surgery (average 2 h) concentrations.

Each blood sample will be collected into standard citrate collection tubes. Tubes will be inverted a minimum of 5 times to ensure proper mixing with anti-coagulant (sodium citrate). Each sample will be labeled with an anonymized patient study number (to de-identify patient information) and sample time. The tubes will be stored on ice bath following sample collection and then centrifuged within 2 hours at 2000g for about 15 min at 4˚C. The subsequent supernatant will be frozen and stored at -70˚C until analyzed. Measurement of TXA and other drug concentrations, renal biomarkers and metabolomics will be performed using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) using previously described methodology. Patients will otherwise receive routine perioperative care. Patient follow up will be to hospital discharge.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Adults > 18 years of age
2. Elective unilateral hip or knee joint replacement

Exclusion Criteria

1. Contraindication to TXA (e.g., allergy, thrombophilia, tretinoin)
2. Advanced liver disease (>2-fold rise in liver enzymes, as this may alter PK analysis)
3. Anti-coagulant use within the last 1-4 days prior (depends on anticoagulant, prior to the day of surgery)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I; Participants with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 (and dialysis)	Drug: Tranexamic acid; Participants in both groups will be given single intravenous bolus of TXA 20 mg/kg over 15 min after induction of spinal (or other regional technique) or general anesthesia as per standard of care.; Other Names: CYKLOKAPRON; trans-4 (aminomethyl) cyclohexanecarboxylic acid
Experimental: Group II; Participants with GFR ≥ 60 mL/min/1.73m2	Drug: Tranexamic acid; Participants in both groups will be given single intravenous bolus of TXA 20 mg/kg over 15 min after induction of spinal (or other regional technique) or general anesthesia as per standard of care.; Other Names: CYKLOKAPRON; trans-4 (aminomethyl) cyclohexanecarboxylic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Plasma TXA Concentration - Total Body Clearance	Measurement of serial blood plasma TXA concentration to build a pharmacokinetic model and dosing regimens for patients within both groups. Curve-stripping of the plasma TXA concentration data according to the 2-compartment model was used to calculate a single value for the measure per participant, which was then averaged.	Collected at 5/15/30/60/90/180/360/540 minutes after bolus
Blood Plasma TXA Concentration - Area Under the Concentration-time Curve	Measurement of serial blood plasma TXA concentration to build a pharmacokinetic model and dosing regimens for patients within both groups. Curve-stripping of the plasma TXA concentration data according to the 2-compartment model was used to calculate a single value for the measure per participant, which was then averaged.	Collected at 5/15/30/60/90/180/360/540 minutes after bolus
Blood Plasma TXA Concentration - Elimination Rate Constant	Measurement of serial blood plasma TXA concentration to build a pharmacokinetic model and dosing regimens for patients within both groups. Curve-stripping of the plasma TXA concentration data according to the 2-compartment model was used to calculate a single value for the measure per participant, which was then averaged.	Collected at 5/15/30/60/90/180/360/540 minutes after bolus
Blood Plasma TXA Concentration - Volume of Central Compartment	Measurement of serial blood plasma TXA concentration to build a pharmacokinetic model and dosing regimens for patients within both groups. Curve-stripping of the plasma TXA concentration data according to the 2-compartment model was used to calculate a single value for the measure per participant, which was then averaged.	Collected at 5/15/30/60/90/180/360/540 minutes after bolus
Blood Plasma TXA Concentration - Steady State Volume of Distribution	Measurement of serial blood plasma TXA concentration to build a pharmacokinetic model and dosing regimens for patients within both groups. Curve-stripping of the plasma TXA concentration data according to the 2-compartment model was used to calculate a single value for the measure per participant, which was then averaged.	Collected at 5/15/30/60/90/180/360/540 minutes after bolus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative Blood Loss and Transfusion	intraoperative measurement of blood loss	Assessed intraoperatively on the day of surgery
% Change in Pre- and Postoperative Hemoglobin	perioperative value of hemoglobin. The % change is calculated as the postoperative hemoglobin minus preoperative hemoglobin, and reported as a percentage of pre-operative hemoglobin. Negative values indicate a reduction in hemoglobin.	Perioperative
Postoperative Creatinine	postoperative value of creatinine	Collected within 24 hours after surgery
Postoperative eGFR	postoperative value of the estimated glomerular filtration rate	Collected within 24 hours after surgery
In-hospital Mortality	death occurring during the hospital stay	Baseline until hospital discharge (up to 7 days after surgery)
Hospital Length of Stay	duration of hospitalization	Baseline until hospital discharge (up to 7 days after surgery)

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Angela Jerath, Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• Yang Q, He J, Peng HB, Wen B, Idestrup C, Ravi B, Murnaghan J, McCarron A, Hadley H, Shin H, Kaustov L, Wong J, Lin Y, Choi S, Orser BA, Van Der Vyver M, Safa B, Pang KS, Jerath A. Tranexamic Dosing for Major Joint Arthroplasty in Adult Patients with Chronic Kidney Disease: A Pharmacokinetic Study and New Dosing Regimen. Anesthesiology. 2025 May 1;142(5):863-873. doi: 10.1097/ALN.0000000000005397. Epub 2025 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Actual): October 26, 2022
• Study Completion (Actual): October 26, 2022

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Total Knee Arthroplasty; Total Hip Arthroplasty; Tranexamic Acid; Dosing; TXA; Anti-fibrinolytic
• Additional Relevant MeSH Terms: Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Cyclohexanecarboxylic Acids; Tranexamic Acid
• Other Study ID Numbers: 1567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified participants data collected during this trial that underlie the results reported in the publication(s) will be available upon request after publication of the primary results.
• IPD Sharing Time Frame: Data will be available upon request immediately after publication of the primary results. No end date.
• IPD Sharing Access Criteria: Direct request to PI. Anyone who wishes to access the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No