Single Versus Multi-Dose Oral Tranexamic Acid in Patients at High Risk for Blood Transfusion After Total Joint Arthroplasty

As tranexamic acid (TXA) becomes more prevalent, all patients are receiving the same dose regardless of their pre-operative risk of transfusion. Therefore the aim of the study is to determine whether or not repeated dosing of oral TXA reduces the post-operative reduction in hemoglobin, hematocrit, number of transfusions, and post-operative blood loss following primary TKA and THA surgeries in patients with low pre-operative hematocrit and high risk for transfusion. The investigators hypothesize that a multi-dose TXA regimen will significantly minimize post-operative blood loss and transfusion requirements compared to the use of a single dose regime.

Study Overview

• Status: Withdrawn
• Conditions: Arthritis; Anemia; Total Knee Arthroplasty; Total Hip Arthroplasty
• Intervention / Treatment: Drug: Conventional Oral TXA (Tranexamic Acid); Drug: Multi-Dose Oral TXA (Tranexamic Acid)

Detailed Description

Total joint arthroplasty is associated with the risk of moderate to significant blood loss. Because TXA has been shown to significantly reduce the need for blood products during total joint replacement, it is now the standard of care at many institutions. Oral and intravenous TXA are equivalent, but oral TXA is cheaper and allows for ease of repeat dosing. Although low preoperative hemoglobin is a risk factor for transfusion, no studies that have compared standard TXA dosing to risk stratified dosing of TXA. The investigators hypothesize that a multi-dose TXA regimen will significantly minimize post-operative blood loss and transfusion requirements compared to the use of a single dose regimen.

At the pre-operative clinic appointment and before the day of surgery, the study staff will assess the potential subject's eligibility. Once eligibility is established, the potential subject will be approached regarding their participation in this clinical trial. The investigators will provide 48 hours before the date of surgery to allot for questions and consideration of the Informed Consent document. Once all patient questions have been answered, patients willing to be in the study will sign the Informed Consent. Patients will be randomized, via standard randomization tables that provide a 1:1 distribution of subjects between the two groups through blocked randomization, no later than the morning of surgery to either of the two treatment groups: Conventional Oral TXA Group or Multi-Dose Oral TXA Group.

• Study Type: Interventional
• Phase: Phase 4

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 and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• older than 18 years
• scheduled for a primary cemented TKA or cementless THA
• preoperative hematocrit less than 36%

Exclusion Criteria:

• Known allergy to TXA
• acquired disturbances of color vision
• refusal of blood products
• pre-operative use of anticoagulant therapy within five days before surgery
• a history of arterial or venous thrombotic disease (including a history of Deep Vein Thrombosis, Pulmonary Embolus, Cerebrovascular accident or Transient ischemic attack)
• pregnancy, breastfeeding
• major co-morbidities (myocardial infarction or stent placement within one year, severe pulmonary disease, renal impairment, or hepatic failure)
• undergoing a revision TKA, revision THA, hip resurfacing, or Unicompartmental Knee Arthroplasty
• younger than 18 years old
• decline to participate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Oral TXA, Total Hip Arthroplasty (THA); THA patients will be given three 650mg tablets of oral TXA 2 hours prior to incision with three 250mg tablets of ascorbic acid (oral TXA placebo) given 6 hours postoperatively and a final 750mg ascorbic acid dose given the morning of postoperative day 1.	Drug: Conventional Oral TXA (Tranexamic Acid); Three 650mg tablets of oral TXA 2 hours prior to incision with three 250mg tablets of ascorbic acid (oral TXA placebo) given 6 hours postoperatively and a final 750mg ascorbic acid dose given the morning of postoperative day 1.
Active Comparator: Conventional Oral TXA, Total Knee Arthroplasty (TKA); TKA patients will be given three 650mg tablets of oral TXA (Tranexamic Acid) 2 hours prior to incision with three 250mg tablets of ascorbic acid (oral TXA placebo) given 6 hours postoperatively and a final 750mg ascorbic acid dose given the morning of postoperative day 1.	Drug: Conventional Oral TXA (Tranexamic Acid); Three 650mg tablets of oral TXA 2 hours prior to incision with three 250mg tablets of ascorbic acid (oral TXA placebo) given 6 hours postoperatively and a final 750mg ascorbic acid dose given the morning of postoperative day 1.
Experimental: Multi-Dose Oral TXA, Total Hip Arthroplasty (THA); THA patients will be given three 650mg tablets of oral TXA 2 hours prior to incision with a second 1950mg oral TXA dose given 6 hours postoperatively and a final 1950mg oral TXA dose given the morning of postoperative day 1.	Drug: Multi-Dose Oral TXA (Tranexamic Acid); Three 650mg tablets of oral TXA 2 hours prior to incision with a second 1950mg oral TXA dose given 6 hours postoperatively and a final 1950mg oral TXA dose given the morning of postoperative day 1.
Experimental: Multi-Dose Oral TXA, Total Knee Arthroplasty (TKA); TKA patients will be given three 650mg tablets of oral TXA 2 hours prior to incision with a second 1950mg oral TXA dose given 6 hours postoperatively and a final 1950mg oral TXA dose given the morning of postoperative day 1.	Drug: Multi-Dose Oral TXA (Tranexamic Acid); Three 650mg tablets of oral TXA 2 hours prior to incision with a second 1950mg oral TXA dose given 6 hours postoperatively and a final 1950mg oral TXA dose given the morning of postoperative day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients transfused	Number of patients transfused per each of the 4 treatment arms	Post-operative and before discharge from hospital (inpatient), < 30 days from surgery
Number of units Packed Red Blood Cells (PRBCs) transfused	Number of units Packed Red Blood Cells (PRBCs) transfused per each of the 4 treatment arms	Post-operative and before discharge from hospital (inpatient), < 30 days from surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative reduction in hemoglobin and hematocrit		Post-operative and before discharge from hospital (inpatient), < 30 days from surgery
Calculated blood loss	Based on predicted blood volume and hemoglobin balance	Post-operative and before discharge from hospital (inpatient), < 30 days from surgery
Cost comparison	Cost differences resulted from differences in the blood transfusion rate, length of hospital stay, and management of complications as well as from the cost of the TXA itself	Post-operative and before discharge from hospital (inpatient), < 30 days from surgery
Complications	Deep Vein Thrombosis, Pulmonary Embolus, return to the Operating Room within 30 days, superficial or deep infection, and cerebrovascular accident, transient ischemic attack or Myocardial Infarction	Post-operative and before discharge from hospital (inpatient), < 30 days from surgery

Collaborators and Investigators

• Sponsor: Rush University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 16060110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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