Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery
Condition: Deep Vein Thrombosis; Pulmonary Embolism
MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Venous Thrombosis
Intervention: Enoxaparin; Apixaban; Enoxaparin-matching placebo; Apixaban-matching placebo
Intervention description: 40 mg, administered once daily by subcutaneous injection, for 12 days; 2.5 mg, administered twice daily as tablets, for 12 days; Administered once daily by subcutaneous injection; Oral tablet administered twice daily
Intervention MeSH terms: Enoxaparin; Enoxaparin sodium; Apixaban
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3221.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prevention of deep vein thrombosis and pulmonary embolism after total knee replacement surgery

Summary:

      The purpose of this study is to learn whether apixaban prevents the development of blood
      clots in the leg (deep vein thrombosis) and lung (pulmonary embolism), which sometimes occur
      after knee replacement surgery, and to compare the efficacy of apixaban with that of
      enoxaparin (Lovenox®) in the prevention of these clots. The safety of apixaban will also be
      studied.
    

Eligibility criteria:

        Key Inclusion Criteria

          -  Patients scheduled for either elective unilateral or same-day bilateral total knee
             replacement surgery (TKR) or a revision of at least 1 component of a TKR

          -  Patients willing and able to undergo bilateral ascending contrast venography

        Key Exclusion Criteria

          -  Known or suspected hereditary or acquired bleeding or coagulation disorders in the
             participant or his or her first-degree relative

          -  Known or suspected history of heparin-induced thrombocytopenia

          -  Known coagulopathy

          -  Active bleeding or at high risk for bleeding

          -  Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days

          -  Active hepatobiliary disease

          -  Alcohol and/or substance abuse within the past year

          -  Any condition for which, in the opinion of the investigator, surgery or administration
             of an anticoagulant was contraindicated

          -  Two consecutive blood pressure readings within 15 to 30 minutes with supine systolic
             blood pressure >180 mm Hg or supine diastolic blood pressure >105 mm Hg

          -  Clinically significant laboratory abnormalities at the enrollment visit:

               -  Hemoglobin <10 g/dL

               -  Platelet count <100,000/mm^3

               -  Creatinine clearance <30 mL/min, as estimated by the method of Cockcroft and
                  Gault

               -  Alanine aminotransferase or aspartate aminotransferase level >2*upper limit of
                  normal (ULN) or a total bilirubin ≥1.5*ULN (unless an alternative causative
                  factor such as Gilbert's syndrome was identified)