Tranexamic Acid in Knee Joint Surgery

Osteoarthritis Clinical Trial

— TRACKS  

Official title:

Tranexamic Acid in Knee Joint Surgery - a Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02278263
• Other study ID #: TRACKS Study
• Status: Completed
• Phase: Phase 4
• Start date: December 2014
• Est. completion date: March 2016

Study information

• Verified date: May 2020
• Source: University of Auckland, New Zealand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Total knee joint replacement surgery can lead to significant blood loss, which can affect recovery after surgery. Tranexamic acid (TXA) is a medication which stops the breakdown of blood clots and therefore prevents blood loss. The optimal use of TXA remains a point of debate. Growing interest in the topical application of TXA (directly into the surgical wound) has been suggested as an alternative way of administering TXA, and may demonstrate similar effectiveness as when it is given intravenously. Therefore, this multicentred, randomized controlled trial, aims to investigate the safety and effectiveness of both topical and intravenous administrations of TXA in total knee joint surgery. The investigators predict that both routes of administration will demonstrate similar results when compared to placebo.

Description:

Postoperative anaemia following elective arthroplasty can lead to prolonged hospital stay, delays in rehabilitation and is often poorly tolerated in patients with cardiovascular disease.(1) Tranexamic acid (TXA) in arthroplasty is used by many orthopaedic surgeons to reduce perioperative blood loss and subsequent transfusion of blood products in elective total hip and knee arthroplasty (THA and TKA). In several reviews, systemic TXA (sTXA) significantly reduces blood loss and transfusion rates when compared to placebo, without an increased risk for venous thromboembolism (VTE).(2-4)

The CRASH-2 study, with over 20,000 randomised trauma patients, has also confirmed the efficacy and safety of TXA in this setting, particularly when given early.(5) The evidence for its use to date is overwhelming and when not contraindicated, should be employed by all arthroplasty units as part of their standard practice. However, despite the vast evidence for its use in arthroplasty some surgeons remain cautious over its safety profile when given systemically. TXA is a synthetic derivative of lysine which is responsible for binding reversibly to plasminogen effectively inhibiting clot degradation.(6) Although, this is not clot promoting, inhibiting clot breakdown theoretically may increase the likelihood of clot formation. This is of real concern for surgeons in patients who have had previous VTE. For this reason, some surgeons have utilised TXA as a topical application directly into the surgical field to reduce systemic absorption and avoid VTE.(7, 8)

TXA administered topically in TKA has also been reported to reduce swelling which may have the advantage of earlier mobility and less pain.(9) In cardiac surgery, TXA has been touted as not only having blood conserving properties via the coagulation pathway but also reduces inflammation via attenuation of the pro-inflammatory cascade.(10, 11)

Based on this rationale, this appears to be a sensible and reasonable route of administration for TXA in this population. However, surgeons should ensure they avoid placing undue risk on patients by altering their use of TXA given the strong evidence for sTXA. Therefore, the purpose of this study is to assess whether topical TXA is effective in reducing blood loss in knee joint replacement surgery, and is as safe and as effective as systemic TXA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients at the participating sites on the waiting list for a unilateral total knee joint replacement

Exclusion Criteria:

• Patients with a history or risk of thrombosis

• Active thromboembolic disease such as deep vein thrombosis, pulmonary embolism and cerebral thrombosis

• Subarachnoid haemorrhage

• Hypersensitivity to tranexamic acid or any of its ingredients.

• Refusal of blood products

• Colour blindness

• Complex hematologic disorders requiring manipulation

• Coagulopathy

• Pregnant and Lactating Women

• Anti-coagulant therapy pre-operatively within 5 days of surgery (warfarin, dabigatran, heparin)

• Severe renal failure (eGFR <29)

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Drug:
• Tranexamic Acid
Given intravenously or topically
• Normal saline (0.9% NaCl)
Administered in all 3 groups

Locations

Country	Name	City	State
New Zealand	Auckland Hospital	Auckland
New Zealand	Manukau Surgery Centre	Auckland
New Zealand	North Shore Hospital	Auckland
New Zealand	Nelson Hospital	Nelson
New Zealand	Tauranga Hospital	Tauranga

Sponsors (1)

Lead Sponsor	Collaborator
Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS

Country where clinical trial is conducted

New Zealand, 

References & Publications (11)

Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total knee replacement: a systematic review and meta-analysis. J Bone Joint Surg Br. 2011 Dec;93(12):1577-85. doi: 10.1302/0301-620X.93B12.26989. Review. — View Citation

Carson JL, Duff A, Berlin JA, Lawrence VA, Poses RM, Huber EC, O'Hara DA, Noveck H, Strom BL. Perioperative blood transfusion and postoperative mortality. JAMA. 1998 Jan 21;279(3):199-205. — View Citation

CRASH-2 collaborators, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011 Mar 26;377(9771):1096-101, 1101.e1-2. doi: 10.1016/S0140-6736(11)60278-X. — View Citation

Gandhi R, Evans HM, Mahomed SR, Mahomed NN. Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Res Notes. 2013 May 7;6:184. doi: 10.1186/1756-0500-6-184. — View Citation

Ishida K, Tsumura N, Kitagawa A, Hamamura S, Fukuda K, Dogaki Y, Kubo S, Matsumoto T, Matsushita T, Chin T, Iguchi T, Kurosaka M, Kuroda R. Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty. Int Orthop. 2011 Nov;35(11):1639-45. doi: 10.1007/s00264-010-1205-3. Epub 2011 Jan 21. — View Citation

Later AF, Sitniakowsky LS, van Hilten JA, van de Watering L, Brand A, Smit NP, Klautz RJ. Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery. J Thorac Cardiovasc Surg. 2013 Jun;145(6):1611-6, 1616.e1-4. doi: 10.1016/j.jtcvs.2012.11.042. Epub 2013 Jan 16. — View Citation

Robertshaw HJ. An anti-inflammatory role for tranexamic acid in cardiac surgery? Crit Care. 2008;12(1):105. doi: 10.1186/cc6210. Epub 2008 Jan 16. — View Citation

Sukeik M, Alshryda S, Haddad FS, Mason JM. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J Bone Joint Surg Br. 2011 Jan;93(1):39-46. doi: 10.1302/0301-620X.93B1.24984. Review. — View Citation

Williams-Johnson JA, McDonald AH, Strachan GG, Williams EW. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2) A randomised, placebo-controlled trial. West Indian Med J. 2010 Dec;59(6):612-24. — View Citation

Wind TC, Barfield WR, Moskal JT. The effect of tranexamic acid on blood loss and transfusion rate in primary total knee arthroplasty. J Arthroplasty. 2013 Aug;28(7):1080-3. doi: 10.1016/j.arth.2012.11.016. Epub 2013 Mar 28. — View Citation

Wind TC, Barfield WR, Moskal JT. The effect of tranexamic acid on transfusion rate in primary total hip arthroplasty. J Arthroplasty. 2014 Feb;29(2):387-9. doi: 10.1016/j.arth.2013.05.026. Epub 2013 Jun 21. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Loss	The loss of haemoglobin (Hb) was then estimated according to the formula: Hb(loss) = Blood volume (BV) x (Hbi-Hbe) x 0.001+Hbt; where Hb (loss) (g) is the amount of Hb lost, Hbi (g/L) the Hb concentration before surgery, Hbe (g/L) is the Hbe concentration on the third day after surgery, and Hbt (g) is the total amount of allogeneic Hb transfused. A unit of banked blood is considered to contain a minimum of 40g Hb (Blood component data sheet, New Zealand Blood Services [NZBS]). All units of blood are processed and stored in a nationally standardised manner. The blood loss (ml) was related to the patient's preoperative Hb value (g/L): Blood loss =1000 x Hb(loss) /Hbi	Post operative day 3
Secondary	Number of Participants Experiencing Symptomatic Venothromboembolic (VTE) Disease	Rates of deep vein thrombosis (DVT) and pulmonary embolus (PE) in each group recorded as a percentage	Postoperatively within 30 days after surgery
Secondary	Number of Participants Receiving Allogenic Blood Transfusion	Those patients receiving blood products. Standardised protocol is as follows: The criterion for transfusion of blood products will be a haemoglobin < 80g/L or a haemoglobin <100g/L in a patient with ischaemic heart disease or with significant symptomatology	Participants will be followed for the duration of their hospital stay expected to be an average of 3-5 days
Secondary	Length of Stay (LOS)	Day of surgery is counted as Day 0.	Average length of stay is expected to be 3 to 5 days
Secondary	Range of Passive Flexion	Range of motion measured in degrees for postoperative days 1 to 3	Days 1-3
Secondary	Range of Active Flexion	Range of motion measured in degrees on postoperative days 1-3	Days 1-3
Secondary	Perioperative Fluid Administration	Intravenous fluid (excluding blood transfusion) given during and first 24 hours after surgery	Day 1