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

NCT ID: NCT07332910

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-20
• Study Completion Date: 2026-06-01

Brief Summary

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.

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.

Conditions

ACL Reconstruction; Hemarthrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Tranexamin acid

This group will receive 1 dose of tranexamic acid during the induction phase, before the surgical tourniquet

Group Type: ACTIVE_COMPARATOR

Tranexamic Acid (TXA)

Intervention Type: DRUG

1 dose of Tranexamic Acid 15 mg/kg

Placebo

This arm will receive NaCl 0,9% at the same volume as calculated for 15mg/kg of tranexamic acid (before the surgical tourniquet)

Group Type: PLACEBO_COMPARATOR

Placebo (NaCl 0,9%)

Intervention Type: DRUG

This arm will receive NaCl 0,9% at the same volume as calculated for 15mg/kg of tranexamic acid

Interventions

Tranexamic Acid (TXA)

1 dose of Tranexamic Acid 15 mg/kg

Intervention Type: DRUG

Placebo (NaCl 0,9%)

This arm will receive NaCl 0,9% at the same volume as calculated for 15mg/kg of tranexamic acid

Intervention Type: DRUG

Other Intervention Names

TXA; Placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Brugmann

OTHER

Sponsor Role: collaborator

Erasme University Hospital

OTHER

Sponsor Role: collaborator

Chirec

OTHER

Sponsor Role: lead

Responsible Party

matthieu clanet

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karim Touihri

Role: PRINCIPAL_INVESTIGATOR

Locations

Chirec Delta

Brussels, , Belgium

Countries

Belgium

Central Contacts

Céline El Haddad, Anesthesia

Role: CONTACT

celineelha@outlook.fr

+32 475466655

Touihri Clanet, Anesthesia

Role: CONTACT

matthieuclanet@gmail.com

Facility Contacts

Céline El Haddad, Anesthesia

Role: primary

celineelha@outlook.fr

+32 475 46 66 55

Matthieu Clanet, Anesthesia

Role: backup

matthieuclanet@gmail.com

References

Prudovsky I, Kacer D, Zucco VV, Palmeri M, Falank C, Kramer R, Carter D, Rappold J. Tranexamic acid: Beyond antifibrinolysis. Transfusion. 2022 Aug;62 Suppl 1:S301-S312. doi: 10.1111/trf.16976. Epub 2022 Jul 14.

Reference Type: BACKGROUND

PMID: 35834488 (View on PubMed)

Alkhatib N, AlNouri M, Abdullah ASA, Ahmad Alzobi OZ, Alkaramany E, Sasaki E, Ishibashi Y. Tranexamic Acid Use in Anterior Cruciate Ligament Reconstruction Decreases Bleeding Complications: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Arthroscopy. 2022 Feb;38(2):506-518.e6. doi: 10.1016/j.arthro.2021.07.030. Epub 2021 Aug 4.

Reference Type: BACKGROUND

PMID: 34358640 (View on PubMed)

Grant AL, Letson HL, Morris JL, McEwen P, Hazratwala K, Wilkinson M, Dobson GP. Tranexamic acid is associated with selective increase in inflammatory markers following total knee arthroplasty (TKA): a pilot study. J Orthop Surg Res. 2018 Jun 18;13(1):149. doi: 10.1186/s13018-018-0855-5.

Reference Type: BACKGROUND

PMID: 29914535 (View on PubMed)

Johns WL, Walley KC, Hammoud S, Gonzalez TA, Ciccotti MG, Patel NK. Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis. Am J Sports Med. 2021 Dec;49(14):4030-4041. doi: 10.1177/0363546521988943. Epub 2021 Feb 25.

Reference Type: BACKGROUND

PMID: 33630652 (View on PubMed)

Fried JW, Bloom DA, Hurley ET, Baron SL, Popovic J, Campbell KA, Strauss EJ, Jazrawi LM, Alaia MJ. Tranexamic Acid Has No Effect on Postoperative Hemarthrosis or Pain Control After Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone Autograft: A Double-Blind, Randomized, Controlled Trial. Arthroscopy. 2021 Jun;37(6):1883-1889. doi: 10.1016/j.arthro.2021.01.037. Epub 2021 Jan 30.

Reference Type: BACKGROUND

PMID: 33529783 (View on PubMed)

Hetsroni I. Tranexamic Acid During Anterior Cruciate Ligament Reconstruction Reduced Drained Blood Volume on Day 1 and Hemarthrosis Up to Day 15 but Did Not Improve Clinical Outcomes at 3 Months. J Bone Joint Surg Am. 2019 Aug 21;101(16):1516. doi: 10.2106/JBJS.19.00514. No abstract available.

Reference Type: BACKGROUND

PMID: 31436663 (View on PubMed)

Goldstein K, Jones C, Kay J, Shin J, de Sa D. Tranexamic Acid Administration in Arthroscopic Surgery Is a Safe Adjunct to Decrease Postoperative Pain and Swelling: A Systematic Review and Meta-analysis. Arthroscopy. 2022 Apr;38(4):1366-1377.e9. doi: 10.1016/j.arthro.2021.10.001. Epub 2021 Oct 14.

Reference Type: BACKGROUND

PMID: 34655767 (View on PubMed)

Mousavi H, Akbari-Aghdam H, Entezari R. The effect of tranexamic acid injection during anterior cruciate ligament reconstruction surgery on postoperative bleeding, pain and swelling. Eur J Orthop Surg Traumatol. 2023 Apr;33(3):639-644. doi: 10.1007/s00590-022-03318-8. Epub 2022 Jul 2.

Reference Type: BACKGROUND

PMID: 35779145 (View on PubMed)

Ma R, Wu M, Li Y, Wang J, Wang W, Yang P, Wang K. The comparative efficacies of intravenous administration and intra-articular injection of tranexamic acid during anterior cruciate ligament reconstruction for reducing postoperative hemarthrosis: a prospective randomized study. BMC Musculoskelet Disord. 2021 Jan 26;22(1):114. doi: 10.1186/s12891-021-03990-7.

Reference Type: BACKGROUND

PMID: 33499848 (View on PubMed)

Felli L, Revello S, Burastero G, Gatto P, Carletti A, Formica M, Alessio-Mazzola M. Single Intravenous Administration of Tranexamic Acid in Anterior Cruciate Ligament Reconstruction to Reduce Postoperative Hemarthrosis and Increase Functional Outcomes in the Early Phase of Postoperative Rehabilitation: A Randomized Controlled Trial. Arthroscopy. 2019 Jan;35(1):149-157. doi: 10.1016/j.arthro.2018.07.050.

Reference Type: BACKGROUND

PMID: 30611343 (View on PubMed)

Cen L, Liu H, Li M, Zhang YF, Zhang HJ, Huang ZY. Intraoperative tranexamic acid reduces postoperative haemarthrosis and improves early functional outcomes in double-bundle anterior cruciate ligament reconstruction. J Orthop. 2024 Dec 10;65:51-56. doi: 10.1016/j.jor.2024.12.005. eCollection 2025 Jul.

Reference Type: BACKGROUND

PMID: 39801905 (View on PubMed)

Tan TK, Ng KT, Lim HJ, Radic R. Effect of tranexamic acid in arthroscopic anterior cruciate ligament repair: A systematic review and meta-analysis of randomised clinical trials. J Orthop Surg (Hong Kong). 2021 May-Aug;29(2):23094990211017352. doi: 10.1177/23094990211017352.

Reference Type: BACKGROUND

PMID: 34027721 (View on PubMed)

Alaia MJ, Gipsman AM. Editorial Commentary: The Benefits of Tranexamic Acid May Outweigh Risks in Arthroscopy and Sports Medicine. Arthroscopy. 2021 Apr;37(4):1334-1336. doi: 10.1016/j.arthro.2021.01.027.

Reference Type: BACKGROUND

PMID: 33812531 (View on PubMed)

Nugent M, May JH, Parker JD, Kieser DC, Douglas M, Pereira R, Lim KS, Hooper GJ. Does Tranexamic Acid Reduce Knee Swelling and Improve Early Function Following Arthroscopic Meniscectomy? A Double-Blind Randomized Controlled Trial. Orthop J Sports Med. 2019 Aug 29;7(8):2325967119866122. doi: 10.1177/2325967119866122. eCollection 2019 Aug.

Reference Type: BACKGROUND

PMID: 31497612 (View on PubMed)

Na Y, Jia Y, Shi Y, Liu W, Han C, Hua Y. Administration of Tranexamic Acid to Reduce Intra-articular Hemarthrosis in ACL Reconstruction: A Systematic Review. Orthop J Sports Med. 2022 Jan 28;10(1):23259671211061726. doi: 10.1177/23259671211061726. eCollection 2022 Jan.

Reference Type: BACKGROUND

PMID: 35111862 (View on PubMed)

Lei Y, Xie J, Huang Q, Huang W, Pei F. Additional benefits of multiple-dose tranexamic acid to anti-fibrinolysis and anti-inflammation in total knee arthroplasty: a randomized controlled trial. Arch Orthop Trauma Surg. 2020 Aug;140(8):1087-1095. doi: 10.1007/s00402-020-03442-2. Epub 2020 Apr 6.

Reference Type: BACKGROUND

PMID: 32253548 (View on PubMed)

Other Identifiers

Chirec

Identifier Type: -

Identifier Source: org_study_id