Clinical trial NCT05075200: Tranexamic Acid Dosing for Major Joint Replacement Surgery
Official title: Tranexamic Acid Dosing for Major Joint Replacement Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Arthroplasty, Replacement, Knee
Arthroplasty, Replacement, Hip
Keywords: Total Knee Arthroplasty
Total Hip Arthroplasty
Tranexamic Acid
TXA
Pharmacokinetics
Dosing
Anti-fibrinolytic
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2021-10-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Blood plasma TXA concentration
timeFrame: at baseline and up to 24 hours post-bolus
Secondary outcomes:
measure: Intraoperative blood loss and transfusion
timeFrame: at baseline through study completion, up to 2 days
measure: % reduction in pre- and postoperative hemoglobin
timeFrame: Perioperative
measure: Postoperative creatinine, GFR and other plasma renal biomarkers (for e.g., NGAL, SUPAR, cystatin)
timeFrame: at baseline through study completion, up to 2 days
measure: In-hospital mortality
timeFrame: Until hospital discharge (through study completion, an average of 1 week)
measure: Hospital length of stay
timeFrame: Until hospital discharge (through study completion, an average of 1 week)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Angela Jerath
role: PRINCIPAL_INVESTIGATOR
References: