Subjects undergoing elective total knee replacement surgery
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subjects must be willing and able to give written informed consent. Target population 2) Subjects undergoing either elective unilateral or same day bilateral total knee replacement or a revision of at least one component of a total knee replacement. 3) Subject must be willing and able to undergo bilateral ascending contrast venography. Age and Sex 4) Men and women, of any race, at least 18 (or legal age of consent if greater) years of age 5) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the treatment period of the study or for 2 weeks after the last dose of study medication, whichever is longer, in such a manner that the risk of pregnancy is minimized. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Sex and Reproductive Status 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire treatment period of the study or for 2 weeks after the last dose of study medication, whichever is longer 2) Women with a positive pregnancy test on enrollment or prior to study drug administration 3) Women who are pregnant or breastfeeding Medical History and Concurrent Diseases 5) Hereditary (first degree) or acquired bleeding or coagulation disorder 6) Known or suspected history of heparin-induced thrombocytopenia 7) Need for ongoing treatment with a parenteral or oral anticoagulant 8) Known coagulopathy 9) Active bleeding or at high risk for bleeding 10) Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days 11) Two consecutive blood pressure readings within 15-30 minutes with supine SBP >180 mm Hg or supine DBP > 105 mm Hg (i.e., initial reading above the limit is confirmed by a second reading) 12) Active hepatobiliary disease 13) Alcohol and/or substance abuse within the past year 14) Any condition, in the opinion of the Investigator, for which surgery or administration of an anticoagulant is contraindicated. Physical and Laboratory Test Findings 15) Clinically significant enrollment visit laboratory abnormalities • Hemoglobin 2 X ULN • Total bilirubin = 1.5 X ULN (unless an alternative causative factor [e.g., Gilbert’s syndrome] is identified). Allergies and Adverse Drug Reactions 16) Hypersensitivity to unfractionated heparin (UFH), low molecular weight heparin (LMWH), porcine products, or iodinated contrast medium (for venogram). Prohibited Therapies and/or Medications 17) Current use of dextrans or fibrinolytics 18) Treatment with medications affecting coagulation or platelet function unless they can be withdrawn as follows: • Unfractionated heparin, LMWH, warfarin (or any other VKA), glycoprotein IIb/IIIa inhibitors (e.g., abciximab, eptifibatide, tirofiban) at least 4 days before surgery • Clopidogrel, ticlopidine, dipyridamole, sulfinpyrazone at least 7 days before surgery • Non-selective NSAIDs with a T1/2 greater than 17 hours (e.g., Piroxicam and Tinoxican) at least 7 days before surgery • Fondaparinux at least 7 days before surgery. • Aspirin >165 mg/day at least 4 days before surgery. Other Exclusion Criteria 19) Prisoners or subjects who are compulsorily detained 20) Subjects who have been previously randomized into an apixaban clinical trial 21) Administration of any investigational drug currently or within 30 days prior to enrollment into this study 22) Subjects unwilling or unable to comply with study medication instructions or study procedures (e.g., bilateral ascending contrast venography) specified in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the effect of oral (PO) apixaban 2.5 mg BID versus subcutaneous (SC) enoxaparin 30 mg q12h on the composite endpoint of adjudicated asymptomatic and symptomatic DVT, non-fatal PE and all-cause death following 12 days of double-blind treatment in subjects undergoing elective total knee replacement surgery.;Secondary Objective: To compare the effect of oral apixaban 2.5 mg BID vs subcutaneous enoxaparin 30 mg q12h on the composite of adjudicated proximal DVT, non-fatal PE and all-cause death after 12 days of double-blind treatment. To assess the effect of oral apixaban 2.5 mg BID versus subcutaneous enoxaparin 30 mg q12h on: • Composite of adjudicated symptomatic DVT, non-fatal and fatal PE during 12 days of double-blind treatment • Adjudicated major bleeding events during 12 days of double-blind treatment • Composite of adjudicated major and clinically relevant non-major bleeding events during 12 days of double-blind treatment • Composite of adjudicated acute myocardial infarction (MI) acute ischemic stroke and other systemic thromboembolic events occurring during the 12 days of double-blind treatment plus the follow up period To assess the overall safety & tolerability of apixaban and enoxaparin during 12 days of double-blind treatment. See Protocol section 2.2 for more secondary objectives;Primary end point(s): Primary efficacy outcome: Composite of adjudicated asymptomatic and symptomatic DVT, non-fatal PE and all-cause death following 12 days of double-blind treatment in subjects undergoing elective total knee replacement surgery. Secondary outcomes: • Composite of adjudicated proximal DVT, non-fatal PE, and all-cause death after 12 days of double-blind treatment following elective total knee replacement surgery • Composite of adjudicated symptomatic DVT, non-fatal and fatal PE during the 12 days of double-blind treatment following elective total knee replacement surgery • Adjudicated major bleeding events | — |
Countries
Denmark, Hungary, Sweden
Outcome results
None listed