Effect of Topical and Intravenous Tranexamic Acid (TXA) on Thrombogenic Markers in Patients Undergoing Knee Replacement (TXA Knee)

The Effect of Topical and Intravenous Tranexamic Acid (TXA) on Thrombogenic Markers in Patients Undergoing Total Knee Replacement

Tranexamic acid (TXA) is a drug that is being used more frequently at the Hospital for Special Surgery to lessen the amount of blood loss after total knee replacement (TKR). It is an anti-fibrinolytic agent, which means that it promotes the formation of blood clots. TXA can be given either intravenously or topically (placed directly on the open wound) before wound closure. Patients with certain medical conditions have been found to have a high risk of thrombosis after being given intravenous TXA, which may lead to serious complications. However, to date, no high-risk patients have been identified for use of topical TXA. This study will look at thrombogenic markers (proteins found in blood that promote clot formation) after TXA is given either intravenously or topically. If the effect on these markers is similar between intravenous and topical use of TXA, then the safety of topical TXA should be questioned. Of note, these markers have never been measured after TXA has been given topically. As a result, this information would be important for the medical community.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Intravenous tranexamic acid; Drug: Topical saline; Drug: Topical tranexamic acid; Drug: Intravenous saline

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

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:

• Patients undergoing primary unilateral total knee replacement with a participating surgeon
• Patients aged 18-80

Exclusion Criteria:

• All patients on steroid therapy regardless of dose, duration, or treatment or those requiring stress-dose steroids preoperatively
• Patients who will require postoperative use of Coumadin, Xarelto, or Plavix
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) within 1 week of surgery
• Hypersensitivity to tranexamic acid
• Renal dysfunction (Creatinine clearance < 40 ml/min)
• Hepatic dysfunction (AST or ALT 2x upper limit of normal)
• Cardiac exclusions: coronary stent, history of myocardial infarction, positive stress test, atrial fibrillation, advanced coronary artery disease
• Advanced chronic obstructive pulmonary disease or advanced interstitial lung disease
• History of venous thromboembolism
• Hypercoagulability (e.g. antiphospholipid syndrome, genetic hypercoagulability with or without prior venous thromboembolism)
• History of stroke or transient ischemic attack

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous tranexamic acid; Patients will receive 1g tranexamic acid in 100mL solution intravenously in the operating room before inflation of the tourniquet. They will again receive the same IV solution in the post-anesthesia care unit, approximately 3 hours after the first solution was given. They will also receive a 75cc topical saline solution approximately 5 minutes before the tourniquet is released.	Drug: Intravenous tranexamic acid; Drug: Topical saline
Experimental: Topical tranexamic acid; Patients will receive 3g tranexamic acid in 75mL solution topically in the operating room, approximately 5 minutes before the tourniquet is released. It will sit for 5 minutes before the solution is suctioned off by the surgeon. They will also receive 2 intravenous saline solutions: one in the operating room before inflation of the tourniquet, and one in the post-anesthesia care unit 3 hours after the first solution was given.	Drug: Topical tranexamic acid; Drug: Intravenous saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Plasmin Anti-plasmin (PAP) - Marker of Fibrinolysis	Levels of PAP will be measured in peripheral blood and wound drainage at 4 hours after tourniquet release.	4 hours after tourniquet release

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation	Systemic PAP blood level measured at the following time points - Intraoperative - Before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release	before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release
Levels of Tranexamic Acid		Intraoperative (before cementing), 1 hour after tourniquet release (TQR), 4 hours after tourniquet release(TQR)
Calculated Postoperative Blood Loss		Duration of inpatient hospital stay (average of 3 days)
Levels of Hemoglobin		1 hour after tourniquet release, POD 1, POD 2
Levels of Hematocrit		1 hour after tourniquet release, POD 1, POD 2
Constavac Blood Drainage	A wound drain is connected to a Constavac system, which postoperatively collects, filters, and allows for reinfusion of the patient's own blood. Shed blood passes through an internal prefilter and is collected in a reservoir.	4 hours after tourniquet release
Incidence of Thrombosis (DVT/PE)		Postoperative day 14 (2 weeks after surgery)
Patients Who Had 1 Unit of Blood Transfusion Administered		Duration of inpatient hospital stay (average of 3 days)
Time to Physical Therapy Discharge		During Hospital Stay
Length of Hospital Stay		Length of Hospital Stay
Levels of IL-6 in Blood		Intraoperative, 1 hour post Tourniquet Release (TQR), 4 hour post Tourniquet Release (TQR)
Levels of Plasmin Anti-plasmin (PAP) - Marker of Fibrinolysis	Levels of PAP will be measured in peripheral blood and wound drainage	Intraoperative, 1 hour post Tourniquet Release (TQR)
Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation in Wound Blood	The values for the wound blood levels are given as the count of patients who had a level above the threshold of >3600 pmol/L.	Intraoperative, 4 hour post Tourniquet Release (TQR)

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Kethy Jules-Elysee, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: September 1, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (Estimate): September 3, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 12, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Total Knee Arthroplasty; Total Knee Replacement; Tranexamic Acid
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 2015-210