Tranexamic Acid Dosing for Major Joint Replacement Surgery

NCT05075200 | Completed Phase 2 Results

• 1 other identifier: 1567
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip

Keywords

Total Knee Arthroplasty; Total Hip Arthroplasty; Tranexamic Acid; TXA; Pharmacokinetics; Dosing; Anti-fibrinolytic

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Intraoperative Blood Loss and Transfusion

  Assessed intraoperatively on the day of surgery

• % Change in Pre- and Postoperative Hemoglobin

  Perioperative

• Postoperative Creatinine

  Collected within 24 hours after surgery

• Postoperative eGFR

  Collected within 24 hours after surgery

• In-hospital Mortality

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

Study Arms (2)

Group I

EXPERIMENTAL

Participants with glomerular filtration rate (GFR) \< 60 mL/min/1.73m2 (and dialysis)

Drug: Tranexamic acid

Group II

EXPERIMENTAL

Participants with GFR ≥ 60 mL/min/1.73m2

Drug: Tranexamic acid

Interventions

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.

Also known as: CYKLOKAPRON, trans-4 (aminomethyl) cyclohexanecarboxylic acid

Group I; Group II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 39878614 DERIVED

MeSH Terms

Interventions

Tranexamic Acid

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Dr. Angela Jerath
• Organization: Sunnybrook Health Sciences Centre

angela.jerath@sunnybrook.ca

416-480-4864

Study Officials

• Angela Jerath

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The main objective of this prospective observational study is to assess TXA blood concentrations in patients requiring major arthroplasty surgery with varied preoperative renal function. We will use this information to create new dosing guidelines for patients undergoing major arthroplasty surgery.

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: October 12, 2021
• Study Start: December 14, 2021
• Primary Completion: October 26, 2022
• Study Completion: October 26, 2022
• Last Updated: December 9, 2025
• Results First Posted: December 9, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available upon request immediately after publication of the primary results. No end date.
• Access Criteria: Direct request to PI. Anyone who wishes to access the data.

Locations

CA (1)