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Completed

NCT Number: NCT05075200

Tranexamic Acid Dosing for Major Joint Replacement Surgery

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.

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Key information

Conditions

Arthroplasty, Replacement, Knee Arthroplasty, Replacement, Hip

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults > 18 years of age
  • Elective unilateral hip or knee joint replacement

Exclusion criteria

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

Treatment and study plan

Tranexamic Acid

Drug

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

Primary outcomes

  1. Blood Plasma TXA Concentration - Total Body Clearance

    Time frame: Collected at 5/15/30/60/90/180/360/540 minutes after bolus

    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.

  2. Blood Plasma TXA Concentration - Area Under the Concentration-time Curve

    Time frame: Collected at 5/15/30/60/90/180/360/540 minutes after bolus

    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.

  3. Blood Plasma TXA Concentration - Elimination Rate Constant

    Time frame: Collected at 5/15/30/60/90/180/360/540 minutes after bolus

    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.

  4. Blood Plasma TXA Concentration - Volume of Central Compartment

    Time frame: Collected at 5/15/30/60/90/180/360/540 minutes after bolus

    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.

  5. Blood Plasma TXA Concentration - Steady State Volume of Distribution

    Time frame: Collected at 5/15/30/60/90/180/360/540 minutes after bolus

    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.

Secondary outcomes

  1. Intraoperative Blood Loss and Transfusion

    Time frame: Assessed intraoperatively on the day of surgery

    intraoperative measurement of blood loss

  2. % Change in Pre- and Postoperative Hemoglobin

    Time frame: Perioperative

    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.

  3. Postoperative Creatinine

    Time frame: Collected within 24 hours after surgery

    postoperative value of creatinine

  4. Postoperative eGFR

    Time frame: Collected within 24 hours after surgery

    postoperative value of the estimated glomerular filtration rate

  5. In-hospital Mortality

    Time frame: Baseline until hospital discharge (up to 7 days after surgery)

    death occurring during the hospital stay

  6. Hospital Length of Stay

    Time frame: Baseline until hospital discharge (up to 7 days after surgery)

    duration of hospitalization

Sponsors and collaborators

Lead sponsor

Sunnybrook Health Sciences Centre

Other

Registry information

Acronym: TXA-Dosing

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Oct 12, 2021
Registry last updated
Dec 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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