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Osteoarthritis, KneePhase 4NCT02458729

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

A Phase 4 study testing Tranexamic Acid 5%,5ml/amp (intraoperative), Tranexamic Acid 5%,5ml/amp (3 hours after operation) and 0.9% Normal Saline (intraoperative) in people with Osteoarthritis, Knee, run by Chang Gung Memorial Hospital at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 50 to 80 years
Conditions the study is for
Osteoarthritis, Knee
What is being tested?
Tranexamic Acid 5%,5ml/amp (intraoperative), Tranexamic Acid 5%,5ml/amp (3 hours after operation) and 0.9% Normal Saline (intraoperative)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
294 participants
Where
1 siteTaiwan
Study dates
Aug 2012to Jul 2014
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

  • Kaohsiung Chang Gung Memorial Hospital

    Koahsiung, Taiwan

Other trials in Taiwan

About this study

Official title: 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.

Read the 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.

Being tested
Tranexamic Acid 5%,5ml/amp (intraoperative), Tranexamic Acid 5%,5ml/amp (3 hours after operation), 0.9% Normal Saline (intraoperative), 0.9% Normal Saline (3 hours after operation), rivaroxaban (10mg)
Keywords
Tranexamic Acid, Total Knee Arthroplasty, Rivaroxaban
Medical subject headings
Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tranexamic Acid 5%,5ml/amp (intraoperative)Drug

    Also called Transamine

    tranexamic acid 1g administered intravenously five minutes before deflation of the tourniquet

  • Tranexamic Acid 5%,5ml/amp (3 hours after operation)Drug

    Also called Transamine

    tranexamic acid 1g administered intravenously 3 hours after operation

  • 0.9% Normal Saline (intraoperative)Drug

    Also called 0.9% sodium chloride

    0.9% Normal Saline 20ml administered intravenously five minutes before deflation of the tourniquet

  • 0.9% Normal Saline (3 hours after operation)Drug

    Also called 0.9% Normal Saline

    0.9% Normal Saline 20ml administered intravenously 3 hours after operation

  • rivaroxaban (10mg)Drug

    Also called Xarelto

    Oral rivaroxabam (10mg) QD on PostOp Day 1 to 14

Study groups in NCT02458729
Study groupRoleWhat they receive
Placebo GroupPlacebo comparatorPrimary 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
Receives: Drug: 0.9% Normal Saline (intraoperative); Drug: 0.9% Normal Saline (3 hours after operation); Drug: rivaroxaban (10mg)
One-dose TXA GroupActive comparatorPrimary 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
Receives: Drug: Tranexamic Acid 5%,5ml/amp (intraoperative); Drug: 0.9% Normal Saline (3 hours after operation); Drug: rivaroxaban (10mg)
Two-dose TXA GroupActive comparatorPrimary 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
Receives: Drug: Tranexamic Acid 5%,5ml/amp (intraoperative); Drug: Tranexamic Acid 5%,5ml/amp (3 hours after operation); Drug: rivaroxaban (10mg)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality

    Primary efficacy outcome is the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or all-cause mortality

    Measured: within 15 days after surgery (2 days after the last dose of rivaroxaban )

  2. Incidence of major bleeding after the first dose of rivaroxaban and all death related to postoperative bleedings

    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

    Measured: within 15 days after surgery (2 days after the last dose of rivaroxaban )

Secondary outcomes (4)

  1. Incidence of major venous thromboembolism

    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

    Measured: within 15 days after surgery (2 days after the last dose of rivaroxaban

  2. Secondary safety outcome was composite of any non-major bleeding and all wound complications after operation

    Non-major bleeding including hemorrhagic wound complications (excessive wound hematoma or bleeding at the surgical site

    Measured: within 15 days after surgery (2 days after the last dose of rivaroxaban

  3. Incidence of wound complications after surgery

    composite of hematoma, superficial wound infection, and deep infection requiring return to surgery

    Measured: within 30 days of the procedure

  4. Total blood loss after surgery

    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

    Measured: From the operation to the postoperative day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2015 (estimated)
  2. Study startAug 2012
  3. Primary completionJul 2014
  4. Study completionJul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
294 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02458729
Sponsor's protocol ID
NMRPG8B6181
Status last verified
May 2015
First submitted
28 May 2015
Last updated
1 Jun 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Petaja J, Myllynen P, Myllyla G, Vahtera E. Fibrinolysis after application of a pneumatic tourniquet. Acta Chir Scand. 1987 Nov-Dec;153(11-12):647-51.

    PubMed 3124428

  • Kambayashi J, Sakon M, Yokota M, Shiba E, Kawasaki T, Mori T. Activation of coagulation and fibrinolysis during surgery, analyzed by molecular markers. Thromb Res. 1990 Oct 15;60(2):157-67. doi: 10.1016/0049-3848(90)90294-m.

    PubMed 2149215

  • Hiippala S, Strid L, Wennerstrand M, Arvela V, Mantyla S, Ylinen J, Niemela H. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth. 1995 May;74(5):534-7. doi: 10.1093/bja/74.5.534.

    PubMed 7772427

  • Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999 Jan;81(1):2-10. doi: 10.2106/00004623-199901000-00002.

    PubMed 9973048

  • Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. J Bone Joint Surg Br. 2001 Jul;83(5):702-5. doi: 10.1302/0301-620x.83b5.11745.

    PubMed 11476309

  • Prevention of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). Int Angiol. 1997 Mar;16(1):3-38. No abstract available.

    PubMed 9165356

  • Clagett GP, Anderson FA Jr, Geerts W, Heit JA, Knudson M, Lieberman JR, Merli GJ, Wheeler HB. Prevention of venous thromboembolism. Chest. 1998 Nov;114(5 Suppl):531S-560S. doi: 10.1378/chest.114.5_supplement.531s. No abstract available.

    PubMed 9822062

  • Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. doi: 10.1016/S0140-6736(09)60734-0. Epub 2009 May 4.

    PubMed 19411100

  • Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. doi: 10.1056/NEJMoa076016.

    PubMed 18579812

  • Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):381S-453S. doi: 10.1378/chest.08-0656.

    PubMed 18574271

  • Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, Wheeler HB. Prevention of venous thromboembolism. Chest. 2001 Jan;119(1 Suppl):132S-175S. doi: 10.1378/chest.119.1_suppl.132s. No abstract available.

    PubMed 11157647

  • Jameson SS, Bottle A, Malviya A, Muller SD, Reed MR. The impact of national guidelines for the prophylaxis of venous thromboembolism on the complications of arthroplasty of the lower limb. J Bone Joint Surg Br. 2010 Jan;92(1):123-9. doi: 10.1302/0301-620X.92B1.22751.

    PubMed 20044690

  • Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007 Jan;89(1):33-8. doi: 10.2106/JBJS.F.00163.

    PubMed 17200307

  • Lotke PA. Rivaroxaban for thromboprophylaxis. N Engl J Med. 2008 Nov 13;359(20):2174; author reply 2175-6. No abstract available.

    PubMed 19009675

  • Jensen CD, Steval A, Partington PF, Reed MR, Muller SD. Return to theatre following total hip and knee replacement, before and after the introduction of rivaroxaban: a retrospective cohort study. J Bone Joint Surg Br. 2011 Jan;93(1):91-5. doi: 10.1302/0301-620X.93B1.24987.

    PubMed 21196550

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tranexamic Acid 5%,5ml/amp (intraoperative), Tranexamic Acid 5%,5ml/amp (3 hours after operation) and 0.9% Normal Saline (intraoperative) in people with Osteoarthritis, Knee, run by Chang Gung Memorial Hospital at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 )). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02458729, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2015.

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