The Blood Saving Effect of Tranexamic Acid in Total Knee Arthroplasty With Rivaroxaban as Thromboprophylaxis

May 28, 2015 updated by: Wang Jun-Wen, Chang Gung Memorial Hospital

The Blood Saving Effect and Wound-related Complications of Tranexamic Acid in Mininally Invasive Total Knee Arthroplasty With Rivaroxaban as Thromboprophylaxis

The aim of this study was to conduct a prospective, randomized, double-blind study and assess the efficacy of and safety for thromboprophylaxis of rivaroxaban in total knee arthroplasty patients when tranexamic acid is used for bleeding prophylaxis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Total knee arthroplasty is an effective procedure for end-stage arthritis of the knee in terms of pain relief and functional recovery. However, this procedure is associated with a substantial perioperative blood loss. As high as 69% allogeneic blood transfusion rate was reported in patients receiving total knee arthroplasty when preoperative haemoglabin level was <13 g/dl. Tranexamic acid (TXA), an antifibrinolytic, given intraoperatively, has been reported to be effective in reducing one third of postoperative blood loss in standard total knee arthroplasty. Our previous study showed that TXA reduced total blood loss from 1453mL to 833mL (p<0.001) and the need for transfusion from 20% to 4% (p=0.014) in total knee patients with enoxaparin (Clexane; Glaxo-Smith-Kline, Brentford, United Kindom) for thromboprophylaxis.

In recent years, there have been more effective and practical methods for thrombophylaxis in total hip and knee replacement surgeries. Rivaroxaban is one of the first oral factor Xa inhibitors licensed for this regard. The advantages of rivaroxaban include oral administration, no need to monitor blood levels and no dosing adjustments which are convenient for short hospital stay in contemporary total knee arthroplasty. Its efficacy in preventing venous thromboembolism (VTE) after total knee arthroplasty have been extensitvely investigated in RECORD (Regulation of Coagulation in Orthopaedic surgery to prevent Deep-vein thrombosis and pulmonary embolism) 3 and 4 studies, and the results showed that rivaroxaban 10mg once daily was superior to enoxaparin 40mg subcutaneously once daily or 30mg every 12 hours for 10 to 14 days. Despite of its clinical efficacy in VTE prophylaxis, orthopaedic surgeons are still sceptic in routine use of rivaroxaban in knee and hip surgery and concerned about the increased risk of bleeding complications. A higher reoperation rate regarding wound complications within 30 days of hip and knee replacement in the rivaroxaban group than the tinzaparin group (2.94% versus 1.8%) was reported recently. Similar event has been reported in other studies. However, all these studies did not use TXA as bleeding prophylaxis after hip and knee replacement surgery. The risk of increasing VTE by use of TXA, owing to its antifibrinolytic effects, is the cause of concern.

The aim of this study was to conduct a prospective, randomized, double-blind study and assess the efficacy of and safety for thromboprophylaxis of rivaroxaban in total knee arthroplasty patients when TXA is used for bleeding prophylaxis.

Study Type

Interventional

Enrollment (Actual)

294

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Koahsiung, Taiwan
        • Kaohsiung Chang Gung Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • End-stage arthritis of the knee
  • Failure of medical treatment or rehabilitation
  • Hemoglobin > 10g/dl
  • No use of non-steroid anti-inflammatory agent one week before operation

Exclusion Criteria:

  • Preoperative Hemoglobin ≦10 g/dl
  • History of infection or intraarticular fracture of the affective knee
  • Renal function deficiency (GFR < 55 ml/min/1.73m2)which is relative contraindicated for venography
  • Elevated liver enzyme, history of liver cirrhosis, impaired liver function and coagulopathy (including long-term use anticoagulant)
  • History of deep vein thrombosis, ischemic heart disease or stroke

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Group
Primary total knee replacement with 0.9% normal saline 20ml administration intravenously twice, five minutes before deflation of the tourniquet and 3 hours after operation Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis
Drug: 0.9% Normal Saline (intraoperative)
0.9% Normal Saline 20ml administered intravenously five minutes before deflation of the tourniquet
Other Names:
  • 0.9% sodium chloride
Drug: 0.9% Normal Saline (3 hours after operation)
0.9% Normal Saline 20ml administered intravenously 3 hours after operation
Other Names:
  • 0.9% Normal Saline
Drug: rivaroxaban (10mg)
Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14
Other Names:
  • Xarelto
Active Comparator: One-dose TXA Group
Primary total knee replacement with 1 g Tranexamic Acid 5%,5ml/amp administrated intravenously five minutes before deflation of the tourniquet. and then 0.9% normal saline 20ml administration intravenously 3 hours after operation Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis
Drug: 0.9% Normal Saline (3 hours after operation)
0.9% Normal Saline 20ml administered intravenously 3 hours after operation
Other Names:
  • 0.9% Normal Saline
Drug: rivaroxaban (10mg)
Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14
Other Names:
  • Xarelto
Drug: Tranexamic Acid 5%,5ml/amp (intraoperative)
tranexamic acid 1g administered intravenously five minutes before deflation of the tourniquet
Other Names:
  • Transamine
Active Comparator: Two-dose TXA Group
Primary total knee replacement with 1 g Tranexamic Acid 5%,5ml/amp administrated intravenously twice, five minutes before deflation of the tourniquet and 3 hours after operation Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14 for VTE prophylaxis
Drug: rivaroxaban (10mg)
Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14
Other Names:
  • Xarelto
Drug: Tranexamic Acid 5%,5ml/amp (intraoperative)
tranexamic acid 1g administered intravenously five minutes before deflation of the tourniquet
Other Names:
  • Transamine
Drug: Tranexamic Acid 5%,5ml/amp (3 hours after operation)
tranexamic acid 1g administered intravenously 3 hours after operation
Other Names:
  • Transamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality
Time Frame: within 15 days after surgery (2 days after the last dose of rivaroxaban )
Primary efficacy outcome is the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality
within 15 days after surgery (2 days after the last dose of rivaroxaban )
Incidence of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings
Time Frame: within 15 days after surgery (2 days after the last dose of rivaroxaban )
Primary safety outcome is the composite of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings. Major bleeding was defined as bleeding that was fatal, that involved a critical organ, or that required reoperation or clinically overt bleeding outside the surgical site that was associated with a decrease in the hemoglobin level of 2 g or more per deciliter or requiring infusion of 2 or more units of blood
within 15 days after surgery (2 days after the last dose of rivaroxaban )

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of wound complications after surgery
Time Frame: within 30 days of the procedure
composite of hematoma, superficial wound infection, and deep infection requiring return to surgery
within 30 days of the procedure
Incidence of major venous thromboembolism
Time Frame: within 15 days after surgery (2 days after the last dose of rivaroxaban
The secondary efficacy outcomes include major venous thromboemolism defined as the composite of proximal deep-vein thrombosis, non-fatal pulmonary embolism, and VTE related death
within 15 days after surgery (2 days after the last dose of rivaroxaban
Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation
Time Frame: within 15 days after surgery (2 days after the last dose of rivaroxaban
Non-major bleeding including hemorrhagic wound complications (excessive wound hematoma or bleeding at the surgical site
within 15 days after surgery (2 days after the last dose of rivaroxaban
Total blood loss after surgery
Time Frame: From the operation to the postoperative day 4
Total blood loss was calculated according to Nadler et al., which used maximum postoperative reduction of the Hb level adjust for weight and height of the patient. The formula is as follows, Total blood loss = (Total blood volume x [change in Hb level / preoperative Hb level])x1000+volume transfused
From the operation to the postoperative day 4

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of venographic positive deep-vein thrombosis (any, proximal, distal)
Time Frame: on the second day after last dose of rivaroxaban (POD 15)
on the second day after last dose of rivaroxaban (POD 15)
Incidence of positive finding of pulmonary embolism by computed tomography
Time Frame: on the second day after last dose of rivaroxaban (POD 15)
In case of suspected pulmonary embolism, computed tomography of the chest was performed
on the second day after last dose of rivaroxaban (POD 15)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

May 28, 2015

First Submitted That Met QC Criteria

May 28, 2015

First Posted (Estimate)

June 1, 2015

Study Record Updates

Last Update Posted (Estimate)

June 1, 2015

Last Update Submitted That Met QC Criteria

May 28, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NMRPG8B6181

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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