Randomized Controlled Trial of Tranexamic Acid in Total Knee Arthroplasty: Intravenous vs. Topical

The purpose of this study is to determine whether topical or intravenous administration of tranexamic acid during unilateral total knee replacement is more effective at reducing bleeding in the first 24 hours following surgery. Tranexamic acid is a synthetic drug that has been shown to reduce blood drain output and the need for blood transfusions in both its topical and intravenous forms and is commonly used in orthopedic surgery. We hypothesize that IV and topical administration of tranexamic acid will be equally good at reducing the loss of blood and the need for transfusion immediately following total knee replacement.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Topical Tranexamic Acid; Drug: Intravenous Tranexamic Acid

Detailed Description

This randomized controlled trial compares the blood loss of patients undergoing unilateral total knee replacements who randomly receive either the topical or the intravenous form of tranexmamic acid during surgery. Patients in the intravenous arm of the study will receive 1 gram of tranexamic acid in 10 milliliters of solution prior to inflation of the tourniquet and 1 gram of tranexamic acid in 10 milliliters of solution during closure. For patients in the topical arm of the study, prior to the release of the tourniquet they will receive 3 grams of tranexamic acid in 75ccs of solution directly on the site of the incision.

The primary result measurement will be blood drain output from the knee at 24 hours after surgery.

• Study Type: Interventional
• Enrollment (Actual): 640
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary total knee replacmeent
• Osteoarthritis
• Unilateral

Exclusion Criteria:

• Revision surgery
• Donated preoperative autologous blood
• On chronic anticoagulation medication such as Coumadin, Xarelto, Plavix, or Aspirin (other than 81mg)
• Preoperative hepatic or renal dysfunction
• Diagnosis of inflammatory disease
• Diagnosis of inflammatory arthritis
• Pregnant
• Breastfeeding
• Preoperative hemoglobin <10g/dL
• International Normalized Ratio>1.4
• Abnormal Partial Thromboplastin Time
• Preoperative platelet count of <150,000mm^3
• Creatinine > 1.4

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Topical Tranexamic Acid; 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes. The surgeon will suction away excess solution. The site may be irrigated before or after the tranexamic acid bath as long as the solution is in contact for at least five full minutes. After that, the tourniquet will be released and the rest of the surgery will proceed according to the standard of care.	Drug: Topical Tranexamic Acid; 3 vials of tranexamic acid (1g tranexamic acid in 10cc each) must be mixed in the operating room by the team at the start of surgery with 45cc of saline solution (for a total of 3g tranexamic acid in 75mL solution). This solution will be applied to the open joint surfaces with two 60mL syringes (one with 60mL and one with 15m). The solution will be left in contact with the tissues for five minutes. The surgeon will suction away excess solution. The site may be irrigated before or after the tranexamic acid bath as long as the solution is in contact for at least five full minutes. After that, the tourniquet will be released and the rest of the surgery will proceed according to the standard of care.
Active Comparator: Intravenous Tranexamic Acid; 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.	Drug: Intravenous Tranexamic Acid; 1 vial (1g of IV tranexamic acid in 10mL solution) will be administered prior to inflation of the tourniquet. A second 1g dose of IV tranexamic acid will be given during initiation of the closure after the tourniquet is deflated and during closure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Blood Loss	The amount of blood lost during surgery is the primary outcome measure. Blood loss is determineusing an equation that calculates the patient's blood volume based on their height and weight, then multiplies the patient's blood volume by the change in their hematocrit after surgery compared to before surgery.	during surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drain Output	The amount of blood collected by a drain attached to the knee is measured 24 hours after surgery.	from end of surgery to 24 hours postoperatively
The Number Patients Requiring a Transfusion	TThe number Patients requiring a transfusion over the course of the patient's hospital stay.	over course of hospital stay (averaging three days)

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Collaborators: Mayo Clinic
• Investigators: Principal Investigator: David Mayman, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Actual): December 28, 2015
• Study Completion (Actual): May 16, 2017

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: September 9, 2013
• First Posted (Estimate): September 12, 2013

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: osteoarthritis; total knee replacement; total knee arthroplasty; tranexamic acid; degenerative joint disease
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 12166