Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis and left to sit for two minutes, excess carefully suctioned followed by standard closure with no drains; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. |
|
| Topical | Experimental | Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis with excess carefully suctioned followed by standard closure with no drains; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. |
|
| Systemic | Experimental | Application of 20ml of normal saline topically after implantation of prosthesis with excess carefully suctioned followed by standard closure with no drains; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tranexamic Acid | Drug | Given intravenously or topically |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Number of Participants Receiving Allogenic Blood Transfusion |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jacob T Munro, MBChB, FRACS | Department of Surgery, The University of Auckland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Auckland Hospital | Auckland | New Zealand | ||||
| Manukau Surgery Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9438739 | Background | 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. doi: 10.1001/jama.279.3.199. | |
| 22161917 | Background | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Patients were excluded after consenting to participate, if they failed to receive spinal anaesthesia.
The hospital databases will be searched for eligible patients on the waiting list for unilateral total knee joint replacement. Patients will be approached in the preadmission clinics and then consented on the day of surgery. Recruitment period is to be over 2 years or sooner once we have recruited the final patient (n=150)
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Control | Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Normal saline (0.9% NaCl): Administered in all 3 groups |
| FG001 | Intraarticular | Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Tranexamic Acid: Given intraarticularly Normal saline (0.9% NaCl): Administered in all 3 groups |
| FG002 | Systemic | Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet Tranexamic Acid: Given intravenously Normal saline (0.9% NaCl): Administered in all 3 groups |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Control | Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Normal saline (0.9% NaCl): Administered in all 3 groups |
| BG001 | Intraarticular |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | The number provided here for each group are those patients analyzed after patients had been excluded due to breaches in the study protocol. As stated in the power calculation for this primary outcome, an attrition rate of 15% (ie breaches in study protocol, drop out etc) had been accounted for. Hence the discrepancy. | Posted | Mean | Standard Deviation | mls | Post operative day 3 |
|
30 days
The total number at risk is now consistent with the numbers provided in the participant flow module. This also applies to the 'Other adverse events' data table.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Normal saline (0.9% NaCl): Administered in all 3 groups |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Vascular disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood transfusion | Blood and lymphatic system disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Marinus Stowers | Ko Awatea | +64 276 0044 | 2219 | msto062@aucklanduni.ac.nz |
Not provided
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Normal saline (0.9% NaCl) | Drug | Administered in all 3 groups |
|
|
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 |
| Length of Stay (LOS) | Day of surgery is counted as Day 0. | Average length of stay is expected to be 3 to 5 days |
| Range of Passive Flexion | Range of motion measured in degrees for postoperative days 1 to 3 | Days 1-3 |
| Range of Active Flexion | Range of motion measured in degrees on postoperative days 1-3 | Days 1-3 |
| Perioperative Fluid Administration | Intravenous fluid (excluding blood transfusion) given during and first 24 hours after surgery | Day 1 |
| Auckland |
| New Zealand |
| North Shore Hospital | Auckland | New Zealand |
| Nelson Hospital | Nelson | New Zealand |
| Tauranga Hospital | Tauranga | New Zealand |
| 21196541 | Background | 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. |
| 23651507 | Background | 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. |
| 21439633 | Background | 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. |
| 21702233 | Background | 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. |
| 23541868 | Background | 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. |
| 23790499 | Background | 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. |
| 21253725 | Background | 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. |
| 23332183 | Background | 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. |
| 18254939 | Background | 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. |
| 28662956 | Derived | Stowers MDJ, Aoina J, Vane A, Poutawera V, Hill AG, Munro JT. Tranexamic Acid in Knee Surgery Study-A Multicentered, Randomized, Controlled Trial. J Arthroplasty. 2017 Nov;32(11):3379-3384. doi: 10.1016/j.arth.2017.05.058. Epub 2017 Jun 9. |
Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Tranexamic Acid: Given intraarticularly Normal saline (0.9% NaCl): Administered in all 3 groups |
| BG002 | Systemic | Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet Tranexamic Acid: Given intravenously Normal saline (0.9% NaCl): Administered in all 3 groups |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Preoperative Hb | Mean | Standard Deviation | grams/L |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Preop Hb (number of days prior to surgery date) | Mean | Standard Deviation | days |
|
| OG000 |
| Control |
Application of 20ml of normal saline (NaCl 0.9%) topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Normal saline (0.9% NaCl): Administered in all 3 groups |
| OG001 | Intraarticular | Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Tranexamic Acid: Given intraarticularly Normal saline (0.9% NaCl): Administered in all 3 groups |
| OG002 | Systemic | Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet Tranexamic Acid: Given intravenously Normal saline (0.9% NaCl): Administered in all 3 groups |
|
|
|
| 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 | Logistic regression for categorical/binary outcomes | Posted | Count of Participants | Participants | 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 | Logistic regression for binary outcomes | Posted | Count of Participants | Participants | 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. | Posted | Median | Inter-Quartile Range | days | 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 | Range of passive flexion measured and the data presented here are the averages with standard deviations | Posted | Mean | Standard Deviation | degrees | Days 1-3 |
|
|
|
| Secondary | Range of Active Flexion | Range of motion measured in degrees on postoperative days 1-3 | Range of active flexion measured and the data presented here represent the average active flexion with SD. | Posted | Mean | Standard Deviation | degrees | Days 1-3 |
|
|
|
| Secondary | Perioperative Fluid Administration | Intravenous fluid (excluding blood transfusion) given during and first 24 hours after surgery | Posted | Mean | 95% Confidence Interval | mls | Day 1 |
|
|
|
| 0 |
| 23 |
| 3 |
| 23 |
| EG001 | Intraarticular | Application of 1.5g in 20ml tranexamic acid topically after implantation of prosthesis; application of 15ml of normal saline intravenously at the same time prior to release of tourniquet. Tranexamic Acid: Given intraarticularly Normal saline (0.9% NaCl): Administered in all 3 groups | 2 | 60 | 4 | 60 |
| EG002 | Systemic | Application of 20ml of normal saline topically after implantation of prosthesis; Application of tranexamic acid intravenously (1.5g/15ml) at the same time prior to release of tourniquet Tranexamic Acid: Given intravenously Normal saline (0.9% NaCl): Administered in all 3 groups | 1 | 51 | 5 | 51 |
Not provided
Not provided
| D000077324 |
| Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| Title | Measurements |
|---|---|
|
|
| Day 3 |
|
|
| Day 3 |
|