Extended Oral Tranexamic Acid After Total Knee Arthroplasty

Randomized Control Trial for Oral Extended Tranexamic Acid After Total Knee Arthroplasty

The utilization of intraoperative tranexamic acid (TXA), whether administered intravenously or orally, has become a standard practice in total joint arthroplasty (TJA). Multiple studies have demonstrated the positive impact that TXA application has on clinical outcomes, including decreased blood loss and transfusion rates, decreased early swelling and ecchymosis, improved early recovery, and potentially superior long-term outcomes. Its ability to mitigate risk of blood loss made ambulatory total knee arthroplasty (TKA) safer for patients. The safety of intraoperative TXA use has also been documented. Sabbag et al. showed that TXA does not increase the risk of venous thromboembolism (VTE), even in those patients who are deemed high-risk. Multiple routes of TXA administration have been studied with each route demonstrating effectiveness in reducing blood loss. Findings showed that oral TXA is noninferior to intravenous TXA, though the median time to reach a target concentration is longer via the oral route and bioavailability is lower. With the benefits of intraoperative TXA clearly documented in literature, multiple centers investigated the utilization of extended TXA postoperatively in hopes of enhancing patient safety and reducing length of stay and healthcare cost. However, these studies reported conflicting outcomes and mostly focused on estimated blood loss, instead of patient reported outcomes.

The purpose of this study is to assess the effectiveness and safety of a varying extended oral TXA regimen during the postoperative period. Further, the investigators aim to determine the optimal duration of the TXA regimen to maximize its impact. The investigators hypothesize that an extended oral TXA regimen is safe and effective in improving clinical outcomes in TKA patients.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pain, Postoperative; Osteo Arthritis Knee
• Intervention / Treatment: Drug: Placebo; Drug: Tranexamic acid

Detailed Description

Total Knee Arthroplasty (TKA) is the treatment for end-stage osteoarthritis. Osteoarthritis stands as one of the prevailing chronic health issues globally. Specifically, knee osteoarthritis represents the predominant form of osteoarthritis in more than half of those diagnosed with the condition. With the aging population, there's a projected exponential rise in the annual TKA procedures performed. The ultimate goals of TKA are to improve mobility and quality of life. However, the benefits of TKA come with risks of surgery. According to the American Joint Replacement Registry, 1% of patients experienced at least one complication within 90 days after their surgery. Many efforts have been made to reduce the rate of complications following TKA. Reducing perioperative blood loss and thus reducing the need for postoperative blood transfusion is critical to ensure positive outcomes for TKA patients. Traditionally, preoperative iron therapy, erythropoietin, and autologous blood donation are mitigation strategies used to decrease the need for blood transfusion. In recent years, the intraoperative use of antifibrinolytic medication, such as Tranexamic Acid (TXA), to control blood loss and improve clinical outcomes has gained increased attention.

The utilization of intraoperative tranexamic acid (TXA), whether administered intravenously or orally, has become a standard practice in total joint arthroplasty (TJA). Multiple studies have demonstrated the positive impact that TXA application has on clinical outcomes, including decreased blood loss and transfusion rates, decreased early swelling and ecchymosis, improved early recovery, and potentially superior long-term outcomes. Its ability to mitigate risk of blood loss made ambulatory TKA safer for patients.

The safety of intraoperative TXA use has also been documented. Sabbag et al. showed that TXA does not increase the risk of venous thromboembolism (VTE), even in those patients who are deemed high-risk. Multiple routes of TXA administration have been studied with each route demonstrating effectiveness in reducing blood loss. Findings showed that oral TXA is noninferior to intravenous TXA, though the median time to reach a target concentration is longer via the oral route and bioavailability is lower.

With the benefits of intraoperative TXA clearly documented in literature, multiple centers investigated the utilization of extended TXA postoperatively in hopes of enhancing patient safety and reducing length of stay and healthcare cost. However, these studies reported conflicting outcomes and mostly focused on estimated blood loss, instead of patient-reported outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Campbell Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18 years of age and older.
2. Primary TKA at a Campbell Clinic Surgery Center, with implant at the discretion of the treating surgeon.
3. Willing to participate in the study.
4. Fluent in oral and written English.

Exclusion Criteria:

1. Revision TKA.
2. Preoperative use of anticoagulants (81mg aspirin is allowed).
3. Prior history of deep vein thrombosis.
4. Prior history of cancer (with the exception of non-melanoma/metastatic skin cancers, low-grade non-metastatic benign soft tissue tumors, thyroid cancers and low grade, non-metastatic prostate cancers).
5. Known allergy or hypersensitivity to TXA.
6. Patients who are using combination hormonal contraception.
7. History of seizure disorder.
8. History of adult onset colorblindness.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients will receive 10 doses of microcrystalline cellulose (3 capsules per dose) from postoperative day (POD) 1 to POD 10.	Drug: Placebo; One dose consists of three microcrystalline cellulose capsules.; Other Names: microcrystalline cellulose
Experimental: 3-day tranexamic acid (TXA); Patients will receive three 1950 milligram (mg) doses of Oral TXA (three 650mg capsules per dose) from POD 1 to POD 3 and 7 doses of Placebo from POD 4 to POD 10.	Drug: Placebo; One dose consists of three microcrystalline cellulose capsules.; Other Names: microcrystalline cellulose; Drug: Tranexamic acid; One dose consists of three 650 milligram (mg) capsules, to be taken orally.; Other Names: TXA
Experimental: 10-day TXA; Patients will receive ten 1950mg doses of Oral TXA (three 650mg capsules per dose) from POD 1 to POD 10.	Drug: Tranexamic acid; One dose consists of three 650 milligram (mg) capsules, to be taken orally.; Other Names: TXA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forgotten Joint Score - Knee	The Forgotten Joint Score measures how much the patient is aware of their affected knee during activities of daily living. A score of 0 indicates that the patient is always aware of their affected knee whereas a score of 100 indicates that the patient is not aware of their affected knee during activities of daily living.	Enrollment; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.
Range of Motion	Passive flexion and extension range of motion of the surgical knee will be assessed with a goniometer in degrees.	Enrollment; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement	This questionnaire assesses patients' knee health with 0 representing total disability and 100 represents perfect knee health.	Enrollment; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.
Patient-Reported Outcomes Measurement Information System	This questionnaire assesses patients' overall health and wellbeing with a T-score of 16.2 representing most severe physical impairment and a T-score of 67.7 represents best possible state of health.	Enrollment; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.
Visual Analog Scale	This questionnaire assesses patient's pain level with 0 being no pain at all and 10 being worst pain possible.	Enrollment; postoperative day 1 to postoperative day 14; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.
Opiate pill count	The investigators will record the number of opiate medication taken by the patient and calculate morphine milligram equivalents.	postoperative day 1 to postoperative day 14; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.
Ambulatory aid	The investigators will record the use of ambulatory aid, such as walker.	Enrollment; postoperative day 1 to postoperative day 14; 2-week postoperative; 6-week postoperative; 12-week postoperative; 1-year postoperative.
Adverse Event	The investigators will monitor for adverse events, including but not limited to deep venous thrombosis, and pulmonary embolism.	From signing consent form to completion of 1 year follow up visit.

Collaborators and Investigators

• Sponsor: Campbell Clinic
• Investigators: Principal Investigator: Christopher Holland, MD, MS, Campbell Clinic

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: September 25, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Cyclohexanecarboxylic Acids; Tranexamic Acid; microcrystalline cellulose
• Other Study ID Numbers: 24-10171-FB

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.: No