Intra-articular Tranexamic Acid in the Reduction of Blood Transfusions in Primary Total Hip and Total Knee Arthroplasty

Role of Low Dose Intra-articular Tranexamic Acid in the Reduction of Blood Transfusions in Primary Total Hip and Total Knee Arthroplasty: A Randomized Placebo Controlled Study

This is a randomized, double blinded, controlled trial in patients undergoing elective Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA). The study group will receive intra-articular Tranexamic Acid (TXA) while the control group will receive normal saline placebo.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Tranexamic Acid; Other: Placebo

Detailed Description

The primary purpose of this study is to determine if intra-articular administration of low dose TXA following THA and TKA results in a clinically relevant reduction in blood loss. The secondary purpose is to determine if there is an increased risk of thromboembolic phenomena with the use of TXA following elective THA and TKA. The primary outcome metric will be - drop in hemoglobin following surgery; secondary metrics include blood loss, transfusion rate, d-dimers, troponin levels, symptomatic deep venous thrombosis (DVT) and pulmonary embolism (PE), vascular events (myocardial infarction, stroke), major and minor bleeding, and death.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2K 3S8
      • Concordia Hospital

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:

• with osteoarthritis
• scheduled for elective primary unilateral THR or TKR
• provided informed consent
• can read, write and speak English

Exclusion Criteria:

• history of arterial or venous thromboembolic disease (myocardial infarction, symptomatic ischemic heart disease, atrial fibrillation, cerebrovascular accident, deep-vein thrombosis, pulmonary embolus, or thrombogenic cardiac valvular disease or rhythm disease)
• pre-operative Hg of <120 g/L
• Known allergy to Tranexamic Acid
• Coagulation disorder
• Acquired disturbances of color vision
• Hepatic insufficiency, any history of liver disease
• Renal insufficiency (on dialysis)
• Preoperative prophylactic use of antiplatelet or anticoagulant therapy such as Clopidogrel, Warfarin, dabigatran or Rivaroxaban. This does not include low dose Aspirin (81mg)
• Patients with a history of subarachnoid hemorrhage [20]
• Simultaneous bilateral THA or TKA
• Any contra-indication for spinal anesthesia
• Allergy to Celecoxib, which will be the only nonsteroidal anti-inflammatory drugs (NSAID) used in the multi-modal analgesia regime.
• Retinal vein or retinal artery occlusion
• Female on oral contraceptive pills and/or premenopausal
• Concurrently taking hydrochlorothiazide, desmopressin, sulbactam-ampicillin, carbazochrome, ranitidine and/or nitroglycerin for the duration of the surgery.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic Acid; Intra-articular administration of low dose Tranexamic acid	Drug: Tranexamic Acid; 0.5g Tranexamic Acid in 0.9% Sodium Chloride (study group) will be injected into the joint after final closure through a temporary catheter that is brought out through the incision.; Other Names: DIN#: 02246365, Sandoz Canada Inc.
Placebo Comparator: Placebo; Sodium Chloride	Other: Placebo; 0.9% Sodium Chloride (placebo group) will be injected into the joint after final closure through a temporary catheter that is brought out through the incision.; Other Names: Sodium Chloride solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in hemoglobin during hospital stay	routinely measured post-op day 1 and 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Troponin	Every 6 hours for 24 hours post-op
D-dimer	Post-op day 1 and 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative blood transfusion	documentation of blood transfusion post-operative	During the first 7 days
Major or minor bleeding events		within 90 days of surgery
Self-reported visual disturbances		within 90 days of surgery
Self-reported symptomatic DVT		within 90 days of surgery
Self-reported PE		within 90 days of surgery
Self-reported stroke		within 90 days of surgery
Death		within 90 days of surgery
Intra-operative fluid balance	documentation of the volume of saline fluid via intravenous given to patients	during surgery
Bleeding sources other than the knee or hip (eg: GI bleed)		within 90 days of surgery
post-operative fluid balance	documentation of the volume of saline fluid via intravenous given to patients	within 3- 5 days of surgery

Collaborators and Investigators

• Sponsor: Orthopaedic Innovation Centre
• Investigators: Principal Investigator: Thomas R Turgeon, MD, Concordia Joint Replacement Group

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): December 21, 2016

Study Registration Dates

• First Submitted: March 3, 2015
• First Submitted That Met QC Criteria: March 19, 2015
• First Posted (Estimate): March 20, 2015

Study Record Updates

• Last Update Posted (Actual): April 10, 2017
• Last Update Submitted That Met QC Criteria: April 6, 2017
• Last Verified: September 1, 2016

More Information

Terms related to this study

• 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: B2013-089