Assessment of microbleeding after prophylaxis with enoxaparin or rivaroxaban against venous thromboembolic disease following hip and knee surgery
Assessment of micro-bleeding after prophylaxis with enoxaparin or rivaroxaban against venous thromboembolic disease following hip and knee arthroplasty
Launceston General Hospital
1,060 participants
Jan 1, 2010
Interventional
Conditions
Summary
Anticoagulants are recommended for prevention and treatment of venous thromboembolism (VTE); comprising deep vein thrombosis (DVT) and pulmonary embolism (PE). Without prophylaxis, DVT occurs in 10–40% of general surgical or medical patients. Patients undergoing major orthopaedic surgery are at a higher risk; without prophylaxis, 40–60% of these patients may develop VTE. Guidelines for VTE prevention recommend the routine use of thromboprophylaxis with low molecular weight heparins (LMWHs) or vitamin K antagonists (VKAs) for patients undergoing major orthopaedic surgery; however, the oral VKAs are rarely used for this indication. The American College of Chest Physicians (ACCP) guidelines currently recommend that thromboprophylaxis be continued for at least 14 days after total knee replacement (TKR), and up to 35 days after total hip replacement (THR). LMWHs are effective; however, their long-term use is limited by their parenteral route of administration. VKAs are the only licensed oral anticoagulants and, although they are effective, they have unpredictable pharmacokinetics (PK) and pharmacodynamics (PD), which are affected by drug and food interactions. As a result, VKAs require frequent monitoring and dose adjustment to ensure that their anticoagulant effects remain within the therapeutic range. Advances in the understanding of the coagulation pathway have enabled the development of novel anticoagulants targeting specific enzymes within the coagulation cascade, including Factor Xa (FXa) and Factor IIa. FXa has been identified as a particularly attractive target for effective anticoagulation: by catalysing the conversion of prothrombin to thrombin through the prothrombinase complex, one molecule of FXa results in the generation of more than 1000 thrombin molecules. Therefore, inhibition of FXa activity may block the amplification of thrombin generation, limiting thrombinmediated activation of coagulation and platelets, without affecting existing thrombin levels. Several FXa inhibitors, such as rivaroxaban, apixaban, betrixaban and edoxaban, are currently at advanced stages of development. Rivaroxaban (Bayer Healthcare AG, Wuppertal, Germany) is a novel, oral, direct FXa inhibitor in advanced development for the prevention and treatment of thromboembolic disorders. Rivaroxaban 10 mg orally once-daily (od) has recently received approval by the Therapeutic Goods Administration (TGA). Australia for the prevention of VTE in patients undergoing elective total hip or knee replacement (THR or TKR) surgery. Recent reports showed high efficacy of rivaroxaban compared to different regimen of LMWH in the prevention of VTE in patients undergoing elective total hip or knee replacement (THR or TKR) surgery. A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. However further studies are warranted to establish the safety profile and to assess the effect of different anticoagulants on the post operative microvascular bleeding.
Eligibility
Inclusion Criteria7
- Arthroplasty for knee or hip disease.
- Over 18 years of age.
- Normal baseline platelet count, prothrombin and partial thromboplastin times.
- The patient or legally authorized representative must sign a written informed consent, prior to the procedure according to the Ethics code of conduct. .
- The potentially eligible patient is at high (post-orthopedic surgery) risk of VTE and the treatment plan will include anticoagulation.
- Women of childbearing potential must be using adequate measures of contraception (as determined by the Investigator) to avoid pregnancy and should be highly unlikely to conceive during the study period.
- Women of childbearing potential must have a negative pregnancy test at screen
Exclusion Criteria9
- Surgery for acute fracture (< 4 weeks), septic joint, or extraction arthroplasty.
- Patients with personal history of thromboembolic disease or documented hypercoagulation disease.
- Increased risk of haemorrhage for example gastro-intestinal bleeding, as from active gastric ulcer, or bleeding diathesis; or persistent intestinal or urinary tract bleed.
- Haemorrhagic stroke; brain, spinal, or ophthalmologic surgery in previous 12 months.
- Requires chronic anticoagulation with warfarin.
- Requires chronic platelet function suppressive therapy for coronary or peripheral artery stents.
- Prior adverse reaction to any of the study drugs.
- Pregnant and/or lactating women and women of child bearing potential not using acceptable means of contraception.
- Participation in any other clinical trials involving investigational or marketed products within 30 days prior to entry in the study
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Interventions
Assess thoroughly post-operative micro-bleeding in patients undergoing knee and hip surgery after treatment with the standard prophylaxis with low molecular weight heparin compared to the new oral anti-Xa rivaroxaban for prevention of the post operative development of thrombosis. For the new oral anti-Xa rivaroxaban intervention a) the dose will be once daily 10 mg tablet; b) the duration of administration will be 35 days for hip replacement surgery and 14 days for knee replacement surgery (first dose at 124 hours after wound closure); and c) the mode of administration is oral tablet. In the first 24 hours after surgery we commence an intermittent pneumatic compression (IPC) device for prevention of DVT for all patients and at the same time to avoid unnecessary bleeding.
Locations(1)
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ACTRN12609000762257