Topical Tranexamic Acid for Total Knee Arthroplasty

NCT00985920 | Completed Phase 4 DMC

• 1 other identifier: 070199A
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

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.

Conditions

Surgical Blood Loss; Total Knee Arthroplasty

Keywords

blood loss; postoperative

Outcome Measures

Primary Outcomes (1)

• Calculated blood loss

  Postoperative day 1-3

Secondary Outcomes (7)

• Total prevalence of drug-related adverse events

  one month after the medication/placebo administration

• perioperative packed red blood cell transfusion requirements

  Intraoperative and postoperative day 1-3

• Systemic absorption of TA after topical application into the surgical wound

  1 hr after the surgey (after touniquet release)

• length of hospital stay

  postoperative

• The change in the knee joint range of motion at flexion

  Postoperative day 2

Study Arms (3)

Tranexamic acid, 1.5 g

EXPERIMENTAL

1.5 g of tranexamic acid in 50 cc of normal saline solution is given to the patients.

Drug: tranexamic acid

Tranexamic acid, 3.0 g

EXPERIMENTAL

3.0 g of tranexamic acid in 50 cc of normal saline is given to the patients.

Drug: tranexamic acid

Placebo, saline

PLACEBO COMPARATOR

50 cc of sterile normal saline solution is given to the patients.

Drug: Placebo

Interventions

tranexamic acid DRUG

Patients will receive a solution containing either 1.5g or 3 g of tranexamic acid in 50 ml of normal saline (0.9% sodium chloride) or only 50 ml of saline without TA (placebo). The treatment solution will be prepared under sterile conditions and coded at TWH pharmacy. In the OR the sterile bag containing the solution will be given to the scrub nurse. The contents (50 ml) will be emptied in a sterile surgical bowl. TA or placebo solution (50 ml) will be then applied to the open joint and tissues by the bulb syringe and will be left in contact with the tissues for 5 minutes. Excess solution will be subsequently suctioned by placing the suction tip on the cemented component without touching the joint and surrounding tissues.

Also known as: cyklokapron

Tranexamic acid, 1.5 g; Tranexamic acid, 3.0 g

Placebo DRUG

Patients will receive a solution containing either 1.5g or 3 g of tranexamic acid in 50 ml of normal saline (0.9% sodium chloride) or only 50 ml of saline without TA (placebo). The treatment solution will be prepared under sterile conditions and coded at TWH pharmacy. In the OR the sterile bag containing the solution will be given to the scrub nurse. The contents (50 ml) will be emptied in a sterile surgical bowl. TA or placebo solution (50 ml) will be then applied to the open joint and tissues by the bulb syringe and will be left in contact with the tissues for 5 minutes. Excess solution will be subsequently suctioned by placing the suction tip on the cemented component without touching the joint and surrounding tissues.

Also known as: normal saline

Placebo, saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Blood Loss, Surgical; Hemorrhage

Interventions

Tranexamic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jean Wong, MD, FRCPC

  Staff Anesthesiologist , Assistant Professor, Department of Anesthesia, Toronto Western Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 28, 2009
• First Posted: September 29, 2009
• Study Start: September 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: November 1, 2009
• Last Updated: April 11, 2011

Record last verified: 2011-04

Locations

CA (1)