The primary purpose of this study is to evaluate postoperative pain. Secondary outcomes evaluated in this study will include range of motion (ROM), opioid consumption, and ambulation. Each outcome measure will be evaluated, oral tranexamic acid (TXA) in the experiment arm and placebo in the control arm, after total knee arthroplasty (TKA) at postoperative days 0-3, and weeks 1, 2, 6, and 12.

Randomized controlled trial with 1:1 allocation, selected through computer-based randomization.

This study will review prospectively collected data, including patient demographic information, surgeon, use of oral tranexamic acid (TXA) or placebo regimen, and postoperative outcomes up to 3 months after surgery. Collaboration with Saint Francis' pharmacy team will be performed to ensure appropriate blinded administering of the oral TXA and placebo medication.

This will be a double blinded study, with both patient and surgeon blinded to study group.

6.0 TXA dosing protocol TXA day of surgery [All patients]

• Administer 1-gram IV TXA intraoperatively at the start of the case (hold for history of stent within 1 year of surgery)

  o AND

• Administer 1-gram IV TXA postoperatively before leaving PACU (hold for history of stent within 1 year of surgery)

  o OR

• Exception: Administer 2 grams TXA in 50cc normal saline topically during the case for patients with a history of stent placed within one year of surgery.

TXA postoperative day (POD) 1-3 [Experimental group]

• Administer 1.95 grams oral (3- 650 mg tablets) TXA each morning for three days following surgery.
• Patients discharged home before POD 3 will be sent home with remaining oral TXA doses.

Placebo POD 1-3 [Control group]

• Administer oral placebo (3 tablets) each morning for three days following surgery.
• Patients discharged home before POD 3 will be sent home with remaining oral placebo doses.

Inclusion Criteria:

• - All patients undergoing either manual or robotic primary total knee arthroplasty (TKA)
• Performed by participating Connecticut Joint Replacement Institute (CJRI) surgeons (Dr. Matthew Grosso, Dr. Robert McAllister, Dr. Chad Daniel, Dr. Eric Silverstein, Dr. Alex Dukas, Dr. Michael Joyce, Dr. Brett Wasserlauf).
• Male and female patient age 18-89
• Primary diagnosis of knee osteoarthritis

Exclusion Criteria:

• Revision TKA

• No exclusion based on gender

• Patients <18 and >89 years old

• Exclusion for IV oral tranexamic acid (TXA):

  • TXA allergy - there are NO absolute contraindications for TXA use.
  • History of stent placed within one year of surgery - patient will receive topical TXA as an alternative.

• Exclusion for oral TXA:

  o Actively treated cancer or deep vein thrombosis (DVT)

• Chronic opioid use (opioid use within the 4 weeks prior to surgery)

• Allergies to nonsteroidal Anti-inflammatory drugs (NSAIDs) and acetaminophen

• Patients with clinically significant drug interactions

• Pre-existing neuropathy

• Current or previous venous thrombosis (DVT or venous stasis disease)

• Immuno-compromised secondary to medical condition

• Immune-suppressive medications, chemotherapy

• Pregnancy, breast feeding

• History of pain catastrophizing. Major depressive disorder

• History of suspected or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.

• Currently on a neuroleptic agent [e.g., gabapentin, pregabalin (Lyrica), duloxetine (Cymbalta) etc.].

• Non-English speaking and reading patient populations

• Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that, in the opinion of the investigator, renders the subject medically unstable or complicates the subject's post-operative course.

This will be a double blinded study, with both patient and surgeon blinded to study group.

Collaboration with Saint Francis' pharmacy team will be performed to ensure appropriate blinded administering of the oral TXA and placebo medication.