The Use of Tranexamic Acid in Decreasing Wound Complication in Total Ankle Replacement. A Pilot Randomized Controlled Trial

This study is a randomized, double-blind, placebo-controlled pilot trial designed to determine the feasibility of conducting a definitive multicentre randomized controlled trial evaluating intravenous and topical tranexamic acid (TXA) for reducing postoperative wound complications following primary total ankle replacement (TAR). The trial will also collect preliminary safety and clinical outcome data to estimate the potential effect of TXA on postoperative wound complications.

Patients with ankle arthritis scheduled to undergo primary TAR will be screened for eligibility and enrolled after providing informed consent. Participants will be randomized in a 1:1 ratio to receive either intravenous and topical TXA or placebo (normal saline) administered according to the study protocol. Participants, treating surgeons, clinical staff, outcome assessors, and investigators will remain blinded to treatment allocation throughout the study.

All participants will undergo standard perioperative management and postoperative care as determined by their treating surgeon. Follow-up assessments will occur according to the routine postoperative schedule through six months after surgery. Data collected will include participant demographics, medical history, operative characteristics, study drug compliance, adverse events, and clinical outcomes.

The primary objective of this pilot trial is to determine the feasibility of conducting a definitive multicentre randomized controlled trial. Feasibility outcomes include participant recruitment, protocol adherence, treatment compliance, retention, completeness of follow-up, and completeness of outcome data collection.

Secondary objectives are to obtain preliminary estimates of the effect of intravenous TXA on postoperative wound complications and other clinically relevant outcomes, including surgical site infection, reoperation, blood transfusion, thromboembolic events, hospital readmission, and patient-reported outcome measures. Safety outcomes, including adverse events and serious adverse events, will also be monitored throughout the study.

The results of this pilot study will inform the design and implementation of a future adequately powered multicentre randomized controlled trial evaluating the effectiveness of intravenous TXA in improving outcomes following total ankle replacement.

Inclusion criteria

• Patient undergoing either primary or revision ankle replacement surgery
• Patient is considered to benefit from surgical management at the treating surgeon's discretion
• The patient is willing and able to provide written informed consent
• The patient is willing and able to comply with post-operative rehabilitation protocols and all follow-up visits

Exclusion criteria

• Pregnant or breastfeeding patient
• Uncontrolled diabetes (HgbA1C > 8)
• Known allergy or contraindication for tranexamic acid use including: presence of coronary stents, cerebrovascular event in the last six months, known thromboembolic disorder, hepatic dysfunction, impaired renal clearance, medications with known drug interactions***
• Lateral-based ankle replacement system
• Patient receiving anticoagulation therapy
• Investigator concerns about study compliance
• Medically unfit for surgery or anesthetic
• Acquired color vision problems that are not genetics

• There are potential drug-drug interactions leading to myocardial infarction after coadministration of tranexamic acid with hormonal contraceptives, hydrochlorothiazide, desmopressin, sulbactam-ampicillin, carbazochrome, ranitidine, or nitroglycerin. Therefore, patients on these medications will be excluded.