Tranexamic Acid in Knee Joint Surgery - a Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 5
- 主要终点
- Blood Loss
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All patients at the participating sites on the waiting list for a unilateral total knee joint replacement
排除标准
- •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)
研究组 & 干预措施
Control
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.
干预措施: Normal saline (0.9% NaCl) (Drug)
Topical
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.
干预措施: Tranexamic Acid (Drug)
Topical
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.
干预措施: Normal saline (0.9% NaCl) (Drug)
Systemic
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
干预措施: Tranexamic Acid (Drug)
Systemic
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
干预措施: Normal saline (0.9% NaCl) (Drug)
结局指标
主要结局
Blood Loss
时间窗: Post operative day 3
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
次要结局
- Length of Stay (LOS)(Average length of stay is expected to be 3 to 5 days)
- Range of Active Flexion(Days 1-3)
- Number of Participants Experiencing Symptomatic Venothromboembolic (VTE) Disease(Postoperatively within 30 days after surgery)
- Number of Participants Receiving Allogenic Blood Transfusion(Participants will be followed for the duration of their hospital stay expected to be an average of 3-5 days)
- Range of Passive Flexion(Days 1-3)
- Perioperative Fluid Administration(Day 1)
研究者
Andrew G Hill, MBChB, MD (Thesis), EdD, FACS, FRACS
Professor of Surgery
University of Auckland, New Zealand