Title Image

The TXA 2 Study (Systemic Tranexamic Acid in Shoulder Arthroscopy and Rotator Cuff Repair)

Current Research
The TXA 2 Study (Systemic Tranexamic Acid in Shoulder Arthroscopy and Rotator Cuff Repair)

Background

Stiffness after rotator cuff repair is common and difficult to prevent. The use of Tranexamic acid (“TXA”) may help but high quality studies are needed to support this theory.

Tranexamic acid is a drug that effectively reduces blood loss and helps clot formation in bleeding arteries during surgery. Its safety and benefits have been well documented in major orthopaedic procedures such as hip replacement, knee replacement, trauma and spinal surgery.

The use of TXA in shoulder surgery is becoming more popular and has shown many advantages. Although transfusion and blood loss are not common in shoulder arthroscopy and rotator cuff repair, stiffness after rotator cuff repair surgery can occur, with reported rates in patients ranging from 4.7% to 32.7%. Whilst a variety of factors have been proposed to contribute to post-operative stiffness, prevention of stiffness has been difficult, even with early range of motion protocols 17-23.

Bleeding into joint spaces has been shown to cause acute stiffness and pain as well as incite an immune response that can lead to the thickening and scarring of connective tissue 24-26, but its role in postoperative stiffness has not been established. That said, TXA use has been studied in knee arthroscopy and ACL reconstruction and has shown a reduction in pain and improved early range of motion. This has thought to have been associated with lower bleeding into the joint postoperatively 27.

Currently, no literature exists looking at TXA use in shoulder arthroscopy and rotator cuff repair. The published evidence on TXA use in shoulder surgery is limited to arthroplasty procedures, which shows a decrease in blood loss and drain tube output 12,14,28,29. Therefore, there is a need for more high-level studies to support the use of intravenous TXA in arthroscopic shoulder surgery and rotator cuff repair.

TXA Study (Systemic Tranexamic Acid in Shoulder Arthroplasty

Objectives

  • To test the hypothesis that systemic use of tranexamic acid reduces bleeding and decreases pain and stiffness in patients undergoing shoulder arthroscopy and rotator cuff repair.

Design

This is a randomised controlled study involving 100 patients divided into two groups: one that receives the treatment drug (TXA) and one that receives a placebo (Saline).

Study Procedure

All consecutive patients indicated for elective arthroscopy and rotator cuff repair will be considered eligible. After having read the information sheet and signed the consent form, they will then be blindly randomized* to one of 2 groups: TXA or Control. Baseline patient characteristics such as age, sex, hand dominance and relevant comorbidities will be recorded in a deidentified Patient Data Chart along with rotator cuff tear size (recorded on pre-operative imaging) and pre-operative pain score extracted from the American Shoulder and Elbow Society (ASES) score which is completed as standard by all patients who consult Dr Cass or Dr Young. During the surgical procedure, patients will be administered either intravenous TXA or placebo (saline) and rotator cuff tear size will be confirmed during arthroscopy. Other procedures including biceps treatment, subacromial decompression, ACJ excision and presence of arthritis will also be recorded. Preoperative range of motion, postoperative pain at 72 hours and 2 weeks together with range of motion at 8 and 24 weeks will also be recorded for outcome analysis.
*As each surgeon has different surgical techniques, their patients will be randomised separately.

Inclusion Criteria

  • Patients consented for shoulder arthroscopy and rotator cuff repair
  • Patients who are capable of and have given informed consent to participate in this study

Exclusion Criteria

  • Patients allergic to tranexamic acid
  • Patients with a failed rotator cuff repair requiring revision
  • Patients with irreparable rotator cuff tears
  • Patients with rotator cuff tears requiring augmentation
  • Patients with history of DVT or pulmonary embolism
  • Patients with history of stroke
  • Patients with cardiovascular disease, including coronary disease or peripheral arteriopathy
  • Patients with renal or liver failure
  • Patients with a known coagulopathy
  • Patients who are or may be pregnant
  • Patients that refuse a potential transfusion

Statistical Procedure

Correlation analysis, including univariate and multivariate analyses will be used to determine the correlation between systemic administration of TXA and the selected outcome criteria. P value <0.5 will be considered as statistically significant. All data will be entered into Socrates Orthopaedic Outcomes Software (Ortholink Pty Ltd, Sydney, Australia).

Ethics and Governance

Approved by St Vincent’s Hospital Human Research Ethics Committee to be undertaken at the Mater Hospital Sydney. HREC reference HREC/17/SVH/174.

Approved by North Shore Private Ethics Committee to be undertaken at North Shore Private Hospital. HREC reference NSPHEC 2017-008.

THERAPEUTIC GOODS ADMINISTRATION
TGA Clinical Trial Notification number CT-2017-CTN-02750-1 v2

AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTRY
ANZCTR trial number ACTRN12617001074381p viewable online here:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373335&isReview=true

Status

Recruitment is expected to commence late 2017 with results expected mid 2018.

References

  • Dunn, C. J. & Goa, K. L. Tranexamic acid: a review of its use in surgery and other indications. Drugs 57, 1005–1032 (1999).
  • Huang, F., Wu, Y., Yin, Z., Ma, G. & Chang, J. A systematic review and meta-analysis of the use of antifibrinolytic agents in total hip arthroplasty. Hip Int. J. Clin. Exp. Res. Hip Pathol. Ther. 25, 502–509 (2015).
  • Sukeik, M., Alshryda, S., Haddad, F. S. & Mason, J. M. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J. Bone Joint Surg. Br. 93, 39–46 (2011).
  • Kagoma, Y. K. et al. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb. Res. 123, 687–696 (2009).
  • Zhang, H., Chen, J., Chen, F. & Que, W. The effect of tranexamic acid on blood loss and use of blood products in total knee arthroplasty: a meta-analysis. Knee Surg. Sports Traumatol. Arthrosc. Off. J. ESSKA 20, 1742–1752 (2012).
  • McCormack, P. L. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs 72, 585–617 (2012).
  • Vigna-Taglianti, F. et al. Tranexamic acid for reducing blood transfusions in arthroplasty interventions: a cost-effective practice. Eur. J. Orthop. Surg. Traumatol. Orthopédie Traumatol. 24, 545–551 (2014).
  • Boyle, J. A. & Soric, M. M. Impact of Tranexamic Acid in Total Knee and Total Hip Replacement. J. Pharm. Pract. (2015). doi:10.1177/0897190015621813
  • Huang, F., Wu, D., Ma, G., Yin, Z. & Wang, Q. The use of tranexamic acid to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis. J. Surg. Res. 186, 318–327 (2014).
  • Hill, G. E., Frawley, W. H., Griffith, K. E., Forestner, J. E. & Minei, J. P. Allogeneic blood transfusion increases the risk of postoperative bacterial infection: a meta-analysis. J. Trauma 54, 908–914 (2003).
  • Friedman, R., Homering, M., Holberg, G. & Berkowitz, S. D. Allogeneic blood transfusions and postoperative infections after total hip or knee arthroplasty. J. Bone Joint Surg. Am. 96, 272–278 (2014).
  • Friedman RJ, Gordon E, Butler RB, Mock L, Dumas B. Tranexamic acid decreases blood loss after total shoulder arthroplasty. Journal of Shoulder and Elbow Surgery. Elsevier; 2016 Apr;25(4):614–8.
  • Phan, D. L., Ani, F. & Schwarzkopf, R. Cost Analysis of Tranexamic Acid in Anemic Total Joint Arthroplasty Patients. J. Arthroplasty 31, 579–582 (2016).
  • Gillespie, R., Shishani, Y., Joseph, S., Streit, J. J. & Gobezie, R. Neer Award 2015: A randomized, prospective evaluation on the effectiveness of tranexamic acid in reducing blood loss after total shoulder arthroplasty. J. Shoulder Elbow Surg. 24, 1679–1684 (2015).
  • Jameson, S. S. et al. Venous thromboembolic events are rare after shoulder surgery: analysis of a national database. J. Shoulder Elbow Surg. 20, 764–770 (2011).
  • Dattani, R., Smith, C. D. & Patel, V. R. The venous thromboembolic complications of shoulder and elbow surgery: A systematic review. Bone Jt. J. 95, 70–74 (2013).
  • Brislin KJ, Field LD, Savoie FH. Complications after arthroscopic rotator cuff repair. Arthroscopy. 2007 Feb;23(2):124–8.
  • Papalia R, Franceschi F, Vasta S, Gallo A. Shoulder stiffness and rotator cuff repair. British medical bulletin. 2012;104:163-74. doi: 10.1093/bmb/lds006. Epub 2012 Feb 14.
  • Itoi E, Arce G, Bain GI, Diercks RL, Guttmann D, Imhoff AB, et al. Shoulder Stiffness: Current Concepts and Concerns. Arthroscopy. Elsevier; 2016 Jul;32(7):1402–14.
  • Trenerry K, Walton JR, Murrell G. Prevention of shoulder stiffness after rotator cuff repair. Clin Orthop Relat Res. 2005;&NA;(430):94–9.
  • Huberty DP, Schoolfield JD, Brady PC, Vadala AP, Arrigoni P, Burkhart SS. Incidence and treatment of postoperative stiffness following arthroscopic rotator cuff repair. Arthroscopy. 2009 Aug;25(8):880–90.
  • Tauro JC. Stiffness and rotator cuff tears: incidence, arthroscopic findings, and treatment results. Arthroscopy. 2006 Jun;22(6):581–6.
  • Lee BG, Cho NS, Rhee YG. Effect of two rehabilitation protocols on range of motion and healing rates after arthroscopic rotator cuff repair: aggressive versus limited early passive exercises. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2012;28(1):34–42.
  • Valentino LA. Blood-induced joint disease: the pathophysiology of hemophilic arthropathy. Journal of Thrombosis and Haemostasis. 2010 Jun 24;8(9):1895–902.
  • Safran MR, Johnston-Jones K, Kabo JM. The effect of experimental hemarthrosis on joint stiffness and synovial histology in a rabbit model. Clin Orthop Relat Res. 1994;&NA;(303):280-288.
  • Hoaglund FT. Experimental Hemarthrosis. The Journal of Bone and Joint Surgery. 1967 Mar;49(2):285–98.
  • Karaaslan F, Karaoğlu S, Yurdakul E. Reducing Intra-articular Hemarthrosis After Arthroscopic Anterior Cruciate Ligament Reconstruction by the Administration of Intravenous Tranexamic Acid: A Prospective, Randomized Controlled Trial. The American Journal of Sports Medicine. 2015 Nov;43(11):2720–6.
  • Sun C-X, Zhang L, Mi L-D, Du G-Y, Sun X-G, He S-W. Efficiency and safety of tranexamic acid in reducing blood loss in total shoulder arthroplasty: A systematic review and meta-analysis. Medicine (Baltimore). 2017 Jun;96(22):e7015.
  • Vara AD, Koueiter DM, Pinkas DE, Gowda A, Wiater BP, Wiater JM. Intravenous tranexamic acid reduces total blood loss in reverse total shoulder arthroplasty: a prospective, double-blinded, randomized, controlled trial. Journal of Shoulder and Elbow Surgery. 2017 Feb 3;26(8):1383–9.
  • Snyder SJ (2003) Arthroscopic classification of rotator cuff lesions and surgical decision making. In: Snyder SJ (ed) Shoulder arthroscopy. Lippincott Williams & Wilkins, Philadelphia, pp 201–207
  • National Statement on Ethical Conduct in Human Research (2007) – Updated December 2013 (The National Statement), Commonwealth of Australia, Canberra.

sydney-shoulder-research-institute-projects

Lead Investigator:

Dr Allan Young

Commenced:

September 2017

Category:

Current Projects

In Research - Current

The TXA 2 Study (Systemic Tranexamic Acid in Shoulder Arthroscopy and Rotator Cuff Repair)