Active Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty

Inclusion criteria

• Give written informed consent
• Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, must use contraception
• Undergoing elective, primary unilateral total knee arthroplasty

Exclusion criteria

• Body weight <50 kg
• Patients at increased risk of bleeding. History of intracranial or intraocular bleeding. History of gastrointestinal and/or endoscopically verified ulcer disease within the past year.
• History of excessive intra- or direct post operative bleeding or a traumatic spinal or epidural anesthesia
• Brain, spinal, or ophthalmologic surgery within the past 3 months
• History of clinically significant liver disease in the past year
• Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values

• aPTT or PT or INR >ULN
• Factor IX activity <LLN
• Factor VIII activity, vWF antigen or Ristocetin cofactor activity <0.5 U/mL
• FXI activity <0.3 U/mL
• Urine protein or blood persistently positive by dipstick. In the event of positive test results, eligibility may be confirmed with urine microscopy or 24 hour urine protein measurement as applicable
• ALT or AST >1.5 x ULN
• Total bilirubin >ULN
• Platelet count <150,000 (or history of thrombocytopenia)
• Hypersensitivity to enoxaparin
• Anticipated concomitant use of anticoagulants/antiplatelet agents or the NSAID nimesulide that may affect study outcome or any other drug influencing coagulation (except low dose aspirin and short acting NSAIDs with a half-life <20 hours) at least 7 days before surgery or during treatment with ISIS Rx.
• Anticipated use of indwelling intrathecal or epidural catheters
• Anemia at Screening
• Have any other conditions which could interfere with the patient participating in or completing the study