Study the Anti-inflammatory Effect of Tranexamic Acid When Used in Anterior Cruciate Ligament Reconstruction. (TXA)

December 31, 2025 updated by: matthieu clanet, Chirec

Tranexaminc Acid : Single Dose vs Placebo to Modulate Postoperative Inflammation After ACL Reconstruction : A Prospective, Randomized, Double-blind Trial

Tranexamic acid (TXA) is widely used in orthopedic surgery to reduce perioperative blood loss, particularly in total hip and knee arthroplasty, due to its antifibrinolytic mechanism, low cost, broad availability, and established safety profile. Its use has recently expanded to minimally invasive procedures such as knee arthroscopy and ACL reconstruction, where postoperative hemarthrosis-rather than intraoperative bleeding-is a major cause of pain, swelling, reduced range of motion, delayed rehabilitation, and impaired early recovery.

Randomized trials and meta-analyses in arthroscopic ACL reconstruction show that TXA, administered intravenously, intra-articularly, or both, reduces postoperative hemarthrosis, joint swelling, drainage volume, and early pain, while improving early functional outcomes. These benefits are mainly short term, with no consistent long-term differences, and no increased risk of thromboembolic events. Evidence in arthroscopic meniscectomy is more limited but suggests modest improvements in early recovery, which may still be clinically meaningful given TXA's favorable risk-benefit profile.

Beyond its antifibrinolytic effects, TXA may influence inflammatory pathways by inhibiting plasmin, which is involved in complement activation and inflammatory modulation. However, existing data are conflicting, with reports of both anti- and pro-inflammatory effects depending on surgical context and dosing. Importantly, most arthroscopy studies focus on clinical outcomes rather than systemic inflammation. To date, no study has comprehensively evaluated perioperative inflammatory responses to TXA in arthroscopic knee surgery, making this low-trauma setting an ideal model to investigate its potential inflammatory effects.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Over the past decade, tranexamic acid (TXA) has been widely adopted in orthopedic surgery to reduce perioperative blood loss and transfusion requirements, particularly in total hip and knee arthroplasty. TXA is a synthetic lysine analogue that inhibits the activation of plasminogen to plasmin, thereby preventing fibrin degradation and limiting fibrinolysis. Due to its low cost, wide availability, and well-established safety profile when administered intravenously, TXA is now routinely used in many countries for procedures associated with a high risk of bleeding.

In recent years, interest has expanded beyond major joint replacement toward minimally invasive orthopedic procedures, such as knee arthroscopy and anterior cruciate ligament (ACL) reconstruction. Although these procedures are generally associated with limited intraoperative blood loss, postoperative hemarthrosis remains the most frequent complication of knee arthroscopy and accounts for a substantial proportion of postoperative morbidity. Hemarthrosis has been shown to induce transient histological changes in articular cartilage and synovial tissue and is associated with increased postoperative pain, joint swelling, reduced range of motion (ROM), delayed rehabilitation, and impaired early functional recovery.

Several randomized controlled trials have investigated the role of TXA in arthroscopic knee surgery. In arthroscopic ACL reconstruction, multiple studies and subsequent systematic reviews and meta-analyses have demonstrated that TXA administration-whether intravenous, intra-articular, or combined-reduces postoperative hemarthrosis, joint swelling, drainage volume, and early postoperative pain, while improving early functional outcomes such as ROM and knee scores. These benefits appear most pronounced during the first postoperative weeks, with no consistent differences observed at longer-term follow-up. Importantly, these studies have not demonstrated an increased incidence of thromboembolic events or major complications associated with TXA use.

In the setting of arthroscopic meniscectomy, data are more limited. A double-blind randomized controlled trial evaluating intravenous TXA in routine arthroscopic meniscectomy suggested modest improvements in early functional recovery, particularly during the immediate postoperative period, despite minimal expected blood loss. Editorial commentaries and systematic reviews have emphasized that, although the absolute benefit of TXA in low-risk arthroscopic procedures may be small, even modest reductions in hemarthrosis and early inflammation may be clinically relevant given the low cost and favorable safety profile of the drug.

Beyond its antifibrinolytic properties, increasing experimental and clinical evidence suggests that TXA may exert biological effects on inflammation and coagulation pathways. Plasmin is known to play a role not only in fibrinolysis but also in the activation of the complement system and modulation of inflammatory mediators. By inhibiting plasmin generation, TXA may influence postoperative inflammatory responses. However, the available evidence remains conflicting. While some studies suggest anti-inflammatory effects, others-particularly in major orthopedic procedures such as total knee arthroplasty-have reported paradoxical increases in circulating pro-inflammatory cytokines following TXA administration.

These discordant findings highlight the complexity of the interaction between coagulation, fibrinolysis, and inflammation, and suggest that the effects of TXA on inflammatory pathways may depend on surgical context, tissue trauma, and dosing strategy. Importantly, most existing studies in arthroscopic surgery have focused primarily on clinical outcomes such as hemarthrosis, pain, and function, with very limited assessment of systemic inflammatory markers.

To date, no study has comprehensively evaluated the perioperative inflammatory response to TXA in arthroscopic knee surgery using serial cytokine measurements and integrated inflammatory burden assessment. Arthroscopic procedures, characterized by limited surgical trauma and low baseline inflammatory activation, represent an ideal clinical model to investigate the potential anti-inflammatory-or pro-inflammatory-effects of TXA in a controlled and sensitive manner.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Brussels, Belgium, 1160
        • Chirec Delta
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Céline El Haddad, Anesthesia
        • Sub-Investigator:
          • Matthieu Clanet, Anesthesia
        • Principal Investigator:
          • Karim Touihri, Anesthesia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Adults aged 18 years or older.
  • Male or female patients scheduled for primary anterior cruciate ligament (ACL) reconstruction.
  • Surgery performed under spinal anesthesia, combined with a postoperative adductor canal block for analgesia.
  • American Society of Anesthesiologists (ASA) physical status I or II.
  • Procedure performed by a single, standardized surgical team.
  • Ability to provide written informed consent.

Exclusion Criteria

  • Age under 18 years.
  • Pregnancy or breastfeeding.
  • Preoperative treatment with anticoagulant or antiplatelet therapy that cannot be safely discontinued.
  • Known coagulation disorders or history of abnormal bleeding.
  • Known hypersensitivity or allergy to tranexamic acid.
  • History of seizure disorders or epilepsy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tranexamin acid
This group will receive 1 dose of tranexamic acid during the induction phase, before the surgical tourniquet
Drug: Tranexamic Acid (TXA)
1 dose of Tranexamic Acid 15 mg/kg
Other Names:
  • TXA
Placebo Comparator: Placebo
This arm will receive NaCl 0,9% at the same volume as calculated for 15mg/kg of tranexamic acid (before the surgical tourniquet)
Drug: Placebo (NaCl 0,9%)
This arm will receive NaCl 0,9% at the same volume as calculated for 15mg/kg of tranexamic acid
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-inflammatory response: Variation of IL-6 over 24 hours
Time Frame: 24 hours
To evaluate the effect of a single intravenous dose of tranexamic acid on the perioperative inflammatory response, assessed by serial plasma interleukin-6 (IL-6) concentrations measured preoperatively, at 6 hours, and at 24 hours postoperatively, with quantification of the inflammatory burden using the area under the curve (AUC) over the first 24 postoperative hours.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hidden blood loss
Time Frame: 3 days

To quantify hidden blood loss (HBL) using perioperative hemoglobin and hematocrit measurements obtained preoperatively, at 24 hours, and on postoperative day 3.

Total blood loss (TBL) will be estimated using validated hematocrit-based formulas incorporating postoperative day-3 hematocrit and estimated blood volume, and hidden blood loss will be calculated as HBL = TBL - intraoperative blood loss (IBL).
3 days
Anti-inflammatory response
Time Frame: 24 hours
To characterize the perioperative inflammatory profile associated with tranexamic acid administration by measuring plasma levels of TNF-α, IL-8, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-10, and C-reactive protein (CRP)at baseline, 6 hours, and 24 hours postoperatively.
24 hours
Fibrinolysis
Time Frame: 24 hours
To assess the effect of tranexamic acid on perioperative fibrinolysis, evaluated through serial measurements of D-dimer levels obtained preoperatively, at 6 hours, and at 24 hours postoperatively.
24 hours
Rehabilitation score
Time Frame: 1 week
- KOOS score: Knee Injury and Osteoarthritis Outcome Score - 0 (worse score) - 100 (best score).
1 week
Rehabilitation score
Time Frame: 1 week
IKDC score (International Knee Documentation Committee) - evaluate impact of treatement in everyday activities: 0 (worse score) - 100 (best score).
1 week
Rehabilitation
Time Frame: 1 week
Range of motion: 0-150 % (extension to flexion)
1 week
adverse effect
Time Frame: 1 week

One of these described: Arterial or venous thrombosis, Seizures, Hypersensitivity reactions (including anaphylaxis), Gastrointestinal adverse effects, Acute renal failure 0 = Not described

1 = described
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chirec

Collaborators

Erasme University Hospital
Centre Hospitalier Universitaire Brugmann

Investigators

  • Principal Investigator: Karim Touihri

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 20, 2026

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

December 17, 2025

First Submitted That Met QC Criteria

December 31, 2025

First Posted (Estimated)

January 12, 2026

Study Record Updates

Last Update Posted (Estimated)

January 12, 2026

Last Update Submitted That Met QC Criteria

December 31, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Chirec

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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