Oral Tranexamic Acid After Total Knee Arthroplasty

Prolonged Oral Tranexamic Acid Use in Primary Total Joint Arthroplasty: A Double Blind Randomized Placebo Controlled Trial

This is a prospective, double-blind, randomized controlled trial evaluating the efficacy of oral tranexamic acid (TXA) in total knee arthroplasty (TKA). The study will assess pain, function, and range of motion (ROM) over a 2-year period, with key evaluations at 6 weeks and 90 days postoperatively.

Hypothesis:

Patients receiving 1.95g oral TXA for 3 or 7 days post-op will show improved pain, function, and ROM at 6 weeks and 90 days, with similar blood loss and transfusion rates as the control group.

Study Overview

• Status: Not yet recruiting
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: Control group placebo; Drug: tranexamic acid Oral-Short Arm; Drug: tranexamic acid Oral-Long Arm

Detailed Description

OBJECTIVES:

Purpose:

This is a prospective, double-blinded, randomized control study to evaluate the efficacy and role of oral Tranexamic acid in total knee arthroplasty by assessing pain, function, and range of motion over a 2-year follow-up period.

Hypothesis:

We hypothesize that those given 1.95g oral TXA for 3- and 7-days post-op will have improved pain, function, and range of motion assessed at the 6-week follow-up along with improved range of motion (ROM) at the 90-day follow-up. Additionally, we expect both the control group and the experimental group to have similar blood loss and transfusion rates.

BACKGROUND:

As the rates of primary and revision total knee arthroplasty (TKA) continue to rise in the United States2,3, it is more important than ever to evaluate and improve primary and secondary outcomes as well as costs associated with these procedures. Tranexamic acid (TXA) has been widely used to improve morbidity and mortality in TKA, with substantial evidence demonstrating its efficacy in reducing blood loss6,7,11,12,13 and transfusion rates6,7,12. A meta-analysis done by Drain et al. also showed a significant reduction in periprosthetic joint infection (PJI) and length of stay4,12 in patients receiving any form of intraoperative TXA. Subsequent studies confirmed that TXA is safe for use in TKA, as it does not increase the incidence of complications including thromboembolic events and renal failure, even in high-risk populations5,6.

Recent literature has increasingly focused on comparing oral versus intravenous (IV) TXA in TKA, aiming to reduce costs while maintaining comparable safety and efficacy to the intravenous formulation. Current evidence strongly supports the noninferiority of preoperative oral TXA compared to IV TXA 8,9,10,14. Similar findings have been reported in revision TKA1. However, a key limitation of these studies is that their primary outcomes are often confined to blood loss, transfusion rates, thromboembolic events, and length of stay. Additionally, significant variability exists in the dosage regimens used across these studies.

While previous research has explored different formulations, doses, and delivery timings of TXA1,7,15, there is limited data on the optimal dosing strategy and length of administration for oral TXA. Most studies focus on perioperative administration, with few investigating the use of TXA beyond postoperative day one16,18,19. Some evidence supports extended IV TXA use for improving clinical parameters such as hemoglobin levels, though further research is needed18,19,20.

Currently, there is a lack of literature examining extended oral TXA use in primary TKA. Existing studies have produced conflicting results regarding pain and function outcomes16,21, with inconsistent dosing regimens further complicating efforts to draw firm conclusions.

Further evaluation of oral TXA administration during the perioperative period and beyond could provide valuable insights for enhancing the safety and reducing the costs of outpatient TKA. Establishing an optimal standard oral dose for prolonged TXA use could improve outcomes, support the transition to outpatient care, and provide consistent post-discharge management protocols.

The purpose of this study is to evaluate the efficacy and role of oral TXA in primary TKA by assessing pain, function, and range of motion over a 2-year follow-up period. We hypothesize that mid-term improvements in pain, function, and range of motion will be observed, with improved clinical outcomes such as arch of motion at the 2-year mark.

• Study Type: Interventional
• Enrollment (Estimated): 351
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anne DeBenedetti, MSc; Phone Number: 13124322468; Email: anne.debenedetti@rushortho.com
• Study Contact Backup: Name: Marisa Toschi, BS; Phone Number: 312-432-2455; Email: marisa.toschi@rushortho.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any patient undergoing primary TKA at Rush main hospital or participating ASC
• Willingness to undergo randomization to take medication potentially up to 7 days post op.
• Willing to answer daily questions on pain, functionality and opioid consumption

Exclusion Criteria:

• History of venous thromboembolism, MI, or stroke in the past year
• Patients on any chronic anticoagulation medications besides Aspirin
• Patients with Cancer
• Patients with end stage renal disease that are on dialysis
• Drug allergy to TXA
• Taking oral birth control
• Unable to provide consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral-Short Arm: 1.95g TXA daily POD 1-3; 1.95g TXA daily for post operative days 1-3	Drug: tranexamic acid Oral-Short Arm; 1.95g Tranexamic acid daily for post op days 1 to 3
Active Comparator: Oral-Long Arm; 1.95g TXA daily for post operative days 1-7	Drug: tranexamic acid Oral-Long Arm; 1.95g tranexamic acid daily post op days 1-7
Placebo Comparator: Control Group: Placebo for 3 days post-op; Placebo for 3 days post-op	Drug: Control group placebo; Placebo for 3 days post-op

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint: knee range of motion	Primary Endpoint: Knee ROM	(flexion/extension) at 2 weeks and 6 weeks post op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary" VAS pain scores	Pain scores (VAS)	2 weeks, 6 weeks, and 3 months post op
Secondary: KOOS Jr		2 weeks. 6 weeks, 3 months post op
secondary: EQ-5D-3L functional scores		2 weeks, 6 weeks, and 3 months post op
Adverse events and complications	Any adverse events or complications after surgery	3 months post op

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Investigators: Principal Investigator: Bailey Terhune, MD, Rush University Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: March 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: postoperative pain; tranexamic acid; range of motion; postoperative function
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Molecular Mechanisms of Pharmacological Action; Antifibrinolytic Agents; Fibrin Modulating Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 25031706

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the conclusion of the study, once all participants have completed all parts of the study
• IPD Sharing Time Frame: 6 months following end of study and will last for a year
• IPD Sharing Access Criteria: unending
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes