Arthroplasty, Replacement, KneePhase 2TXA-DosingNCT05075200
Tranexamic Acid Dosing for Major Joint Replacement Surgery
A Phase 2 study testing Tranexamic acid in people with Arthroplasty, Replacement, Knee and Arthroplasty, Replacement, Hip, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthroplasty, Replacement, Knee, Arthroplasty, Replacement, Hip
- What is being tested?
- Tranexamic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteCanada
- Study dates
- 14 Dec 2021to 26 Oct 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults > 18 years of age
- Elective unilateral hip or knee joint replacement
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the 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.
- Being tested
- Tranexamic acid
- Keywords
- Total Knee Arthroplasty, Total Hip Arthroplasty, Tranexamic Acid, TXA, Pharmacokinetics, Dosing, Anti-fibrinolytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic acidDrug
Also called CYKLOKAPRON, trans-4 (aminomethyl) cyclohexanecarboxylic 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.
| Study group | Role | What they receive |
|---|---|---|
| Group I | Experimental | Participants with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 (and dialysis) Receives: Drug: Tranexamic acid |
| Group II | Experimental | Participants with GFR ≥ 60 mL/min/1.73m2 Receives: Drug: Tranexamic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Collected at 5/15/30/60/90/180/360/540 minutes after bolus
Secondary outcomes (6)
Intraoperative Blood Loss and Transfusion
intraoperative measurement of blood loss
Measured: 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.
Measured: Perioperative
Postoperative Creatinine
postoperative value of creatinine
Measured: Collected within 24 hours after surgery
Postoperative eGFR
postoperative value of the estimated glomerular filtration rate
Measured: Collected within 24 hours after surgery
In-hospital Mortality
death occurring during the hospital stay
Measured: Baseline until hospital discharge (up to 7 days after surgery)
Hospital Length of Stay
duration of hospitalization
Measured: Baseline until hospital discharge (up to 7 days after surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2021
- Study start14 Dec 2021
- Primary completion26 Oct 2022
- Study completion26 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Arthroplasty, Replacement, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angela Jerath, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05075200
- Sponsor's protocol ID
- 1567
- Acronym
- TXA-Dosing
- Status last verified
- Feb 2025
- First submitted
- 3 Sep 2021
- Last updated
- 9 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 39878614
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tranexamic Acid Dosing for Major Joint Replacement Surgery
- ClinicalTrials.gov ID
- NCT05075200
- Acronym / sponsor ID
- TXA-Dosing / 1567
- Keywords
- Total Knee Arthroplasty, Total Hip Arthroplasty, Tranexamic Acid, TXA, Pharmacokinetics, Dosing, Anti-fibrinolytic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- 26 Oct 2022 (actual)
- Study completion
- 26 Oct 2022 (actual)
- First posted
- 12 Oct 2021 (actual)
- Results
- Posted 9 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Group I | Experimental | Drug: Tranexamic acidParticipants with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 (and dialysis) |
| Group II | Experimental | Drug: Tranexamic acidParticipants with GFR ≥ 60 mL/min/1.73m2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults > 18 years of age
- Elective unilateral hip or knee joint replacement
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic acidAlso: CYKLOKAPRON, trans-4 (aminomethyl) cyclohexanecarboxylic acidParticipants 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. | Drug | Group I, Group II |
Primary outcome
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.
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.
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.
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.
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.
6 secondary outcomes
Intraoperative Blood Loss and Transfusion
Time frame: Assessed intraoperatively on the day of surgery
% Change in Pre- and Postoperative Hemoglobin
Time frame: Perioperative
Postoperative Creatinine
Time frame: Collected within 24 hours after surgery
Postoperative eGFR
Time frame: Collected within 24 hours after surgery
In-hospital Mortality
Time frame: Baseline until hospital discharge (up to 7 days after surgery)
Hospital Length of Stay
Time frame: Baseline until hospital discharge (up to 7 days after surgery)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39878614Yang 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela Jerath principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tranexamic acid in people with Arthroplasty, Replacement, Knee and Arthroplasty, Replacement, Hip, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Plasma TXA Concentration - Total Body Clearance (time frame: Collected at 5/15/30/60/90/180/360/540 minutes after bolus). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05075200, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.