Weighted Versus Uniform Dose of Tranexamic Acid in Patients Undergoing Primary, Knee Arthroplasty

Weighted Versus Uniform Dose of Tranexamic Acid in Patients Undergoing Primary, Knee Arthroplasty, a Randomized-clinical Trial.

Hypotheses: Primary - A weighted dose of 20 mg/kg of tranexamic acid will be more efficacious than a single uniform dose of 1 gram in primary total knee arthroplasty (TKA) cases. This includes having a greater impact on decreasing blood loss without increasing the occurrence of adverse thromboembolic events in patients undergoing primary, elective total knee arthroplasty.

Secondary - TA will decrease blood loss more effectively in women than in men undergoing this procedure.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis; Intraoperative Bleeding
• Intervention / Treatment: Drug: Females receiving a uniform dose of TA; Drug: Females Tranexamic Acid weighted dose; Drug: Males Weighted Dose TA; Drug: Tranexamic Acid standard dose

Detailed Description

Overall Study Design

Study design and control methods:

This study is designed as a prospective, randomized, double-blinded controlled clinical trial to compare the effect of a single uniform 1 g dose of TA and a single weighted 20 mg/kg dose of tranexamic acid (TA).

Treatment group:

The subjects will be randomly assigned to the uniform dose group or weighted dose group at the time of the surgery via the opening of a randomly selected closed envelope. The patient and the independent reviewer will be blinded as to the dose of TA utilized during the surgery. This information will be linked to a confidential database for later review by the principal investigator.

Treatment allocation:

All eligible patients (i.e., meeting inclusion criteria and no exclusion criteria) will be treated and observed per the research protocol. All patients will maintain the right to refuse participation and receive a specific treatment of the study if desired.

Trial Population

Target population:

The target sample size is 60 patients of each of the uniform and weighted dose groups (120 total). There will be one actively enrolling surgeon (Dr. Brett Levine). The goal is to enroll a total of 120 subjects experiencing joint pain that warrants a TKA. The specific diagnosis for the joint pain will not direct the subjects' assignment or eligibility at the time of surgery. All 120 patients will be enrolled from the office of the primary investigator (Dr. Brett Levine). All indications for TKA will be included unless one of the exclusion criteria is met.

Results from randomized patients will be compared to a historical control arm that did not receive TA in their treatment.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must be male or female of any race
2. Ages 18-80 years old
3. Patients must be undergoing an elective, primary knee arthroplasty
4. Patients must be able to understand and willing to cooperate with study procedures
5. Patients must be able to provide written and verbal informed consent

Exclusion Criteria:

1. Allergy or intolerance to the study materials
2. History of a venous thromboembolic event being treated with life-long anticoagulation
3. Patients with a known congenital thrombophilia
4. Patients who have had a venous thromboembolic event within the 12 months preceding surgery
5. History of any substance abuse or dependence within the last 6 months
6. Failure in collecting a required data point during study
7. Those patients not indicated for knee replacement surgery including, pregnant women, those not cleared medically for the procedure and patients without significant radiographic evidence of degenerative joint disease.
8. Patient using autologous blood transfusion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Females receiving a uniform dose of TA; Women receiving a single dose of 1 gram of TA--includes all women that will get 1 gram dose of the TA during surgery. Postop outcomes wil be measured for comparison, including hemoglobin, hematocrits and blood loss.	Drug: Females receiving a uniform dose of TA; Patients will receive a uniform 1 gm dose of tranexamic acid prior to tourniquet release during a primary TKA.; Other Names: Tranexamic Acid
Active Comparator: Weighted dose of TA in female patients; Female patients receiving a weighted dose of TA. Will include all women that will get a weighted dose of the TA during surgery. Postop outcomes wil be measured for comparison, including hemoglobin, hematocrits and blood loss.	Drug: Females Tranexamic Acid weighted dose; Weighted dose--20mg/kg of the drug will be given; Other Names: TA
Active Comparator: Tranexamic acid weighted dose male; Male patients randomized to the weighted dose of TA. Postop outcomes wil be measured for comparison, including hemoglobin, hematocrits and blood loss.	Drug: Males Weighted Dose TA; Weighted dose--20mg/kg of the drug will be given; Other Names: Transexamic Acid
Active Comparator: Uniform single dose TA male patient; Male patients receiving a single dose (1gram) of TA during TKA. Includes all men that will get 1 gram dose of the TA during surgery. Postop outcomes wil be measured for comparison Postop outcomes wil be measured for comparison, including hemoglobin, hematocrits and blood loss. Patients will be randomized into one of these two groups.	Drug: Tranexamic Acid standard dose; Uniform 1 gram dosing; Other Names: Male TA
No Intervention: Historical Cohort; 25 patients with no TA use in their surgical history. A control group was established from a historical cohort of primary TKAs performed by the senior author (BL), none of which received TA. The most relevant Pubmed ID would be 24997651.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Intra-operative Blood Loss	Record intra-operative blood loss through drain output	Intra-operative, an average of 3 hours
Document Incidences of DVT and Other Thromboembolic Events.	DVT = Deep Venous thrombosis Patients were assessed every 12 hours for development of pain within the lower extremity. Any reported muscle pain was evaluate with a bedside venous ultrasound by an ultrasound technician.	1 year

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Investigators: Study Director: Mark Belkin, BS, Rush University Medical Center

Publications and helpful links

General Publications

• Ralley FE, Berta D, Binns V, Howard J, Naudie DD. One intraoperative dose of tranexamic Acid for patients having primary hip or knee arthroplasty. Clin Orthop Relat Res. 2010 Jul;468(7):1905-11. doi: 10.1007/s11999-009-1217-8. Epub 2010 Jan 9. Erratum In: Clin Orthop Relat Res. 2010 May;468(5):1447.
• Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009 Mar;123(5):687-96. doi: 10.1016/j.thromres.2008.09.015. Epub 2008 Nov 12.
• Husted H, Blond L, Sonne-Holm S, Holm G, Jacobsen TW, Gebuhr P. Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients. Acta Orthop Scand. 2003 Dec;74(6):665-9. doi: 10.1080/00016470310018171.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: May 1, 2012
• First Submitted That Met QC Criteria: July 26, 2012
• First Posted (Estimate): July 27, 2012

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: complications; Blood loss; transfusion rates
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Intraoperative Complications; Blood Loss, Surgical; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 12021202