Tranexamic Acid Dosing for Major Joint Replacement Surgery

Arthroplasty, Replacement, Knee Clinical Trial

— TXA-Dosing  

Official title:

Tranexamic Acid Dosing for Major Joint Replacement Surgery

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05075200
• Other study ID #: 1567
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 14, 2021
• Est. completion date: August 2024

Study information

• Verified date: October 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arthroplasty, Replacement, Hip
• Arthroplasty, Replacement, Knee

Intervention

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.

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood plasma TXA concentration	Measurement of serial blood plasma TXA concentration to build a pharmacokinetic model and dosing regimens for patients within both groups	at baseline and up to 24 hours post-bolus
Secondary	Intraoperative blood loss and transfusion	intraoperative measurement of blood loss	at baseline through study completion, up to 2 days
Secondary	% reduction in pre- and postoperative hemoglobin	perioperative value of hemoglobin	Perioperative
Secondary	Postoperative creatinine, GFR and other plasma renal biomarkers (for e.g., NGAL, SUPAR, cystatin)	perioperative values of creatinine, GFR and other renal biomarkers	at baseline through study completion, up to 2 days
Secondary	In-hospital mortality	death occurring during the hospital stay	Until hospital discharge (through study completion, an average of 1 week)
Secondary	Hospital length of stay	duration of hospitalization	Until hospital discharge (through study completion, an average of 1 week)