Clinical trial NCT00985920: Topical Tranexamic Acid for Total Knee Arthroplasty
Official title: Efficacy of Intraoperative Topical Application of Tranexamic Acid in Reducing Perioperative Bleeding in Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Surgical Blood Loss
Total Knee Arthroplasty
Keywords: blood loss
postoperative
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: The Physicians' Services Incorporated Foundation
First posted: 2009-09-29
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Total knee arthroplasty (TKA), the definitive treatment of osteoarthritis, is often associated with excessive postoperative bleeding due to increased fibrinolysis. Hence, the objective of the proposed study is to determine the role of topical application of tranexamic acid (TA), an anti-fibrinolytic agent, into the knee joint just before closure during TKA to reduce perioperative bleeding. The investigators' hypothesis is that in patients undergoing unilateral primary TKA, intraoperative application of 1.5 g or 3.0g topical TA into the knee joint before closure reduces perioperative bleeding as depicted by a decrement in the maximal drop in hemoglobin concentration following surgery. This proposal describes a randomized, double-blinded, placebo-controlled clinical trial with three arms. The primary outcome is the extent of the postoperative reduction in hemoglobin levels. Secondary outcomes will include transfusion requirements, hospital stay, joint functionality, quality of life and safety of using topical TA. Topical application of TA is a novel intraoperative approach that has not been used or studied in TKA. However if it is effective, it will directly reduce postoperative intra-articular bleeding without subsequent systemic absorption and thromboembolism. In addition, the reduction in microvascular intra-articular bleeding will lead to less pain and infection rates as well as improved surgical functional outcomes.

Detailed description: Three million (1 in 10) Canadians suffer from Osteoarthritis (OA). Total knee arthroplasty (TKA), i.e. knee replacement surgery is the definitive treatment for knee osteoarthritis which alleviates pain and restores physical functioning. However, it can be associated with excessive postoperative bleeding leading to increased mortality and morbidity. The current blood conservation techniques, i.e. preoperative erythropoietin and autologous blood donation, do not reduce bleeding from the surgical site. As a result, many patients require blood transfusion with the associated risks and costs. In TKA, postoperative bleeding is attributed to diffuse microvascular bleeding as a result of increased fibrinolytic activity caused by releasing of the tourniquet which is routinely applied to provide appropriate surgical exposure during surgery. Therefore, tranexamic acid (TA), an antifibrinolytic agent which blocks the dissolution of hemostatic fibrin, can decrease blood loss following TKA. The systemic administration of TA, however, carries the risk of thromboembolic events such as deep vein thrombosis (DVT) or pulmonary embolism (PE). In TKA, this is of greater importance, as the patients are at higher risk of thromboembolic events. Topical application of TA in the surgical field is a cost-effective and simple route of administration that has been shown to reduce bleeding in dental, cardiac, and spine surgeries while minimizing systemic absorption and thromboembolism. Another major advantage of this approach is to prevent diffuse microvascular bleeding at the site of raw tissue surfaces resulting in decreased infection rate, pain, and increased range of motion (ROM) of the knee joints. In spite of these potential benefits, the innovative idea of topical application of TA has not been studied in TKA. However, if it is shown to be efficacious in decreasing postoperative bleeding, it can be incorporated into routine clinical practice with immediate beneficial impacts on patient care and quality of life.

Hypothesis:

In patients undergoing unilateral primary/revision TKA, intraoperative application of 1.5 g or 3 g topical TA into the surgical wound for five minutes before closure reduces perioperative bleeding as depicted by the maximal drop in systemic hemoglobin concentration during the postoperative period.

General Objective:

To study the role of tranexamic acid as a therapeutic tool, applied intraoperatively into the surgical wound, to reduce perioperative blood loss in patients undergoing a unilateral primary/revision TKA.

Specific Objectives:

To determine:

* the efficacy of topical application of TA to reduce perioperative transfusion requirements.
* the safety of topical application of TA (complications such as DVT).
* the systemic absorption of TA after topical application into the surgical wound.
* the impact of postoperative hemoglobin (Hb) reduction on patients' quality of life.
* the impact of topical application of TA on the length of hospital stay.
* the impact of topical application of TA on ROM, pain, and surgical infection rate of the knee joint.
* the incidence of autologous and allogenic blood transfusion in patients receiving the standard.
* multimodal blood conservation techniques for TKA surgery at our institution
* to compare the efficacy and safety of high dose (3 g) of TA versus low dose (1.5 g) of TA.

Eligibility criteria: Inclusion Criteria:

* All adult patients (greater than 18 years old).
* Patients scheduled for primary unilateral total knee arthroplasty.

Exclusion Criteria:

* Allergy to tranexamic acid
* Acquired disturbances of color vision
* Preoperative anemia (hemoglobin \<110 in females; hemoglobin \<120 in males)
* Refusal of blood products (Jehovah's witnesses),
* Preoperative use of anticoagulant therapy - coumadin, heparin within 5 days of surgery, fibrinolytic disorders requiring intraoperative antifibrinolytic treatment,
* Coagulopathy (preoperative platelet count \< 150,000/mm3, INR \>1.4, prolonged PTT (\>1.4 x normal))
* A previous history of thromboembolic disease (e.g. CVA, DVT or PE)
* Pregnancy
* Breastfeeding
* Significant co-morbidities:
* severe ischemic heart disease; NYHA Class III, IV,
* previous myocardial infarction
* severe pulmonary disease, e.g. FEV1\<50% normal,
* plasma creatinine greater than 115 µmol/l in males and more than 100 µmol/l in females
* hepatic failure
* Intraoperative surgical/medical/anesthetic complications occur, e.g. MI, intraoperative bone fracture or neurovascular injury

Primary outcomes:
measure: Calculated blood loss
timeFrame: Postoperative day 1-3
Secondary outcomes:
measure: Total prevalence of drug-related adverse events
timeFrame: one month after the medication/placebo administration
measure: perioperative packed red blood cell transfusion requirements
timeFrame: Intraoperative and postoperative day 1-3
measure: Systemic absorption of TA after topical application into the surgical wound
timeFrame: 1 hr after the surgey (after touniquet release)
measure: length of hospital stay
timeFrame: postoperative
measure: The change in the knee joint range of motion at flexion
timeFrame: Postoperative day 2
measure: The amount of pain at the knee joint measured by a visual scale (VAS)
timeFrame: Postoperative week 6
measure: Health-related quality of life determined by the Western Ontario and Mac Master Universities Osteoarthritis (WOMAC) index score
timeFrame: Postoperative week 6
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Staff Anesthesiologist , Assistant Professor, Department of Anesthesia, Toronto Western Hospital
name: Jean Wong, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: