The Effect of Local and Systemic Tranexamic Acid on Edema and Ecchymosis in Orbital Surgery

The Effect of Local and Systemic Tranexamic Acid on Edema and Ecchymosis in Orbital Surgery - a Prospective, Multicenter, Randomized, Double-blinded, Control Trial

Tranexamic acid (TXA) is a synthetic reversible competitive inhibitor to plasminogen lysine receptor, which prevents plasmin formation and stabilizes the fibrin matrix, thus reducing bleeding. While recent studies have demonstrated the antifibrinolytic benefits of TXA in obstetric and gynecologic conditions, traumatic hemorrhage, cardiac surgery, total knee arthroplasty, and more, there is a paucity of clinical data on TXA use in plastic surgery. The aim of this study is to evaluate the effect of local and systemic TXA on postoperative periocular ecchymosis/edema in orbital surgery.

Study Overview

• Status: Recruiting
• Conditions: Orbital Edema; Orbital Ecchymosis
• Intervention / Treatment: Drug: Tranexamic Acid in NaCl,Iso-Os 1,000 Mg/100 mL (10 Mg/mL) INTRAVEN INTRAVENOUS SOLUTION, PIGGYBACK (ML); Drug: normal saline - injection; Drug: Tranexamic acid injection; Drug: normal saline - intravenous

Detailed Description

Patients, who will be undergoing orbital surgery anyways, will be given the option to participate in the study. Informed consent will be obtained in clinic during the preoperative consultation. On the day of surgery in the preoperative suite, study participants will be randomly allocated to one of three groups via computer-generated random numbers:

Group 1: will receive 1g intravenous tranexamic acid (Pfizer, New York, NY) 20 minutes prior to surgery. Group 2: will receive 1.7 mL of subcutaneous tranexamic acid 100 mg/mL (Pfizer, New York, NY) with local anesthetic to the orbit two minutes prior to incision. Group 3: will receive intravenous normal saline and subcutaneous local anesthetic (i.e. standard procedure) as control group.

Twenty minutes before incision time, all patients will receive an intravenous solution. This will be either saline (placebo, participants in group 2 and 3) or 1g of tranexamic acid (participants in group 1). All operations will be performed using the standard of care technique and surgical instruments. All surgery will be performed under intravenous sedation with local anesthesia. Standard skin marking will be drawn, then the surgeon will inject each patient subcutaneously with either (1) a 5 cc mixture of TXA (100 mg/mL) mixed with 2% lidocaine with epinephrine and 0.5% marcaine with epinephrine in a 1:1:1 ratio (local TXA, Group 2) or (2) normal saline 0.9% sodium chloride mixed with 2% lidocaine with epinephrine and 0.5% marcaine with epinephrine in a 1:1:1 ratio (Group 1, Group 3). Degree of ecchymosis and edema in the postoperative photographs will be assessed separately by two graders. Graders will be blinded to treatment groups, and the photos will be completely deidentified.

Immediately following the procedure, the surgeon will take standardized photographs. The surgeon will also take standardized photographs at the regular 7-day postoperative visit. These photos will be deidentified and analyzed for degree of ecchymosis and edema by two blinded graders who will rate the photos using a standard five point grading scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = profound) as described in the respective outcome measures.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anne Barmettler; Phone Number: 718-920-4609; Email: abarmett@montefiore.org

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: Anne Barmettler, MD; Phone Number: 718-920-4609; Email: abarmett@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing orbital surgery (decompressions, fracture repairs, enucleations, eviscerations, etc.)
• Patients who are at least 18 years of age
• Patients that have the capacity to consent

Exclusion Criteria:

• Any history of previous orbital surgery
• Any patient undergoing multiple simultaneous periocular surgical procedures
• Any patient with active infection
• History of stroke or seizure
• History of bleeding/clotting disorder
• Patients who do not comply with the required postoperative follow-up schedule
• Patients who are allergic to tranexamic acid
• Patients who have taken anticoagulant/antiplatelet agents (including aspirin) within 7 days prior to surgery
• Patients who have periocular ecchymosis or edema prior to surgery

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: IV TXA; 1g intravenous tranexamic acid (Pfizer, New York, NY) 20 minutes prior to surgery	Drug: Tranexamic Acid in NaCl,Iso-Os 1,000 Mg/100 mL (10 Mg/mL) INTRAVEN INTRAVENOUS SOLUTION, PIGGYBACK (ML); 1g IV TXA; Drug: normal saline - injection; 0.9% Normal Saline injection in the orbit
Experimental: Group 2: Local TXA; 1-2mL of subcutaneous tranexamic acid 100 mg/mL (manufactured concentration, Pfizer, New York, NY) mixed with local anesthetic to the orbit two minutes prior to incision	Drug: Tranexamic acid injection; 100 mg/mL (manufactured concentration) local TXA injection in the orbit; Drug: normal saline - intravenous; 0.9% IV Normal Saline
Placebo Comparator: Group 3: Control; Normal saline and subcutaneous local anesthetic to both eyelids (i.e. standard procedure) as control group	Drug: normal saline - injection; 0.9% Normal Saline injection in the orbit; Drug: normal saline - intravenous; 0.9% IV Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of Ecchymosis	Degree of ecchymosis on postoperative day zero (POD0) and postoperative day 7 (POD7) as graded on a 5 point Likert scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = profound) by two independent graders. The two scores will be averaged for inclusion in analysis. Scores will be aggregated to calculate means and standard deviations (SDs) for each group. Higher scores are associated with increased severity of ecchymosis.	0 days and 7 days postoperatively
Degree of Edema	Degree of edema on postoperative day zero (POD0) and postoperative day 7 (POD7) as graded on a 5 point Likert scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = profound) by two independent graders. The two scores will be averaged for inclusion in analysis. Scores will be aggregated to calculate means and standard deviations (SDs) for each group. Higher scores are associated with increased severity of edema.	0 days and 7 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Satisfaction with edema	Patients asked how satisfied they are with their edema postoperatively. Responses will be scored as 0 (not satisfied at all), 1 (somewhat unsatisfied), 2 (neutral), 3 (somewhat satisfied), or 4 (completely satisfied). Responses will be summed and mean scores and standard deviations (SDs) will be reported for each group. Higher scores correlate with increased degree of satisfaction.	7 days postoperatively
Patient Satisfaction with ecchymosis	Patients asked how satisfied they are with their ecchymosis postoperatively. Responses will be scored as 0 (not satisfied at all), 1 (somewhat unsatisfied), 2 (neutral), 3 (somewhat satisfied), or 4 (completely satisfied). Responses will be summed and mean scores and standard deviations (SDs) will be reported for each group. Higher scores correlate with increased degree of satisfaction.	7 days postoperatively
Other side effects	Patients will be asked if they had any seizure, focal weakness, lower extremity pain, difficulty breathing, chest pain, or any emergency room visit (to assess for adverse effects including thromboembolic event or seizure). Responses will be recorded as either "Thromboembolic event occurred" or "Thromboembolic event did not occur." Seizure events will be recorded in the same way. The number of patients with thromboembolic events and/or seizures will be summarized by the study arm.	7 days postoperatively

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Anne Barmettler, Montefiore Medical Center/Albert Einstein College of Medicine

Publications and helpful links

General Publications

• Colomina MJ, Contreras L, Guilabert P, Koo M, M Ndez E, Sabate A. Clinical use of tranexamic acid: evidences and controversies. Braz J Anesthesiol. 2022 Nov-Dec;72(6):795-812. doi: 10.1016/j.bjane.2021.08.022. Epub 2021 Oct 7.
• Kono S, Lee PAL, Kakizaki H, Takahashi Y. Orbital haematoma after orbital fracture repair using silicone, polytetrafluorethylene, and poly-L-lactic acid/hydroxyapatite implants. Br J Oral Maxillofac Surg. 2021 Nov;59(9):1036-1039. doi: 10.1016/j.bjoms.2021.01.002. Epub 2021 Jan 15.
• Paramo R, Cheng T, Malik A, Fan J, Barmettler A. Effect of Tranexamic Acid on Intra- and Postoperative Bleeding in Eyelid Surgery: A Prospective, Randomized, Multicenter, Double-Masked, Control Trial. Ophthalmic Plast Reconstr Surg. 2024 May-Jun 01;40(3):331-335. doi: 10.1097/IOP.0000000000002583. Epub 2024 Apr 12.
• Marous CL, Farhat OJ, Cefalu M, Rothschild MI, Alapati S, Wladis EJ. Effects of Preoperative Intravenous Versus Subcutaneous Tranexamic Acid on Postoperative Periorbital Ecchymosis and Edema Following Upper Eyelid Blepharoplasty: A Prospective, Randomized, Double-Blinded, Placebo-Controlled, Comparative Study. Ophthalmic Plast Reconstr Surg. 2024 Sep-Oct 01;40(5):523-532. doi: 10.1097/IOP.0000000000002633. Epub 2024 Apr 29.
• Artymowicz, A., & Shinder, R. (2022). Effect of subcutaneous tranexamic acid on hemostasis and ecchymosis in dacryocystorhinostomy: A double-blind, placebo-controlled, randomized clinical trial. Poster session presented at the ASOPRS 2022 Conference, Chicago, IL, United States.
• Zilinsky I, Barazani TB, Shenkman B, Weisman O, Farber N, Martinowitz U. Topical Hemostatic-Anesthetic Solution to Reduce Bleeding During Mohs Micrographic Surgery: A Case Control Study. J Drugs Dermatol. 2016 Jul 1;15(7):851-5.
• Horrow JC, Van Riper DF, Strong MD, Grunewald KE, Parmet JL. The dose-response relationship of tranexamic acid. Anesthesiology. 1995 Feb;82(2):383-92. doi: 10.1097/00000542-199502000-00009.
• Schroeder RJ 2nd, Langsdon PR. Effect of Local Tranexamic Acid on Hemostasis in Rhytidectomy. Facial Plast Surg Aesthet Med. 2020 May/Jun;22(3):195-199. doi: 10.1089/fpsam.2020.0061. Epub 2020 Mar 31.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Orbital Surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Ecchymosis; Edema; Organic Chemicals; Pharmaceutical Preparations; Carboxylic Acids; Crystalloid Solutions; Isotonic Solutions; Solutions; Acids, Carbocyclic; Cyclohexanecarboxylic Acids; Tranexamic Acid; Saline Solution
• Other Study ID Numbers: 2024-15945

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plans to share IPD.

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.: No