Factor Xa Inhibitor, PRT054021, Against Enoxaparin for the Prevention of Venous Thromboembolic Events (EXPERT)
Condition: Thromboembolism
MeSH terms: Thromboembolism
Intervention: Betrixaban; Enoxaparin
Intervention description: Capsule; Administered subcutaneously
Intervention MeSH terms: Enoxaparin; Betrixaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Prevention of Venous Thromboembolism

Summary:

      Randomized study of PRT054021 40 mg and 15 mg bid vs. enoxaparin 30 mg q12h for the
      prophylaxis of venous thromboembolic events after unilateral knee replacement surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  • The subject has undergone elective primary unilateral TKR (not unicompartmental).

        Demographic

          -  The subject is between the ages of 18 and 75 years.

          -  If the subject is a woman, she is without reproductive potential (postmenopausal for
             >2 years or after hysterectomy).

          -  The subject weighs between 50 kg (110 lbs) and 120 kg (265 lbs). Laboratory and
             Procedures

          -  The subject is willing and able to undergo unilateral venography. Medications

          -  The subject is willing and able to self-inject enoxaparin or receive injections q12h
             by a caregiver.

        Ethical • The subject is able to read and give written informed consent and has signed an
        informed consent form approved by the Investigator's IRB/IEC.

        Exclusion Criteria:

          -  Disease Related

               -  Major medical and/or surgical condition which may impair oral drug absorption or
                  metabolism.

               -  Immobilization for 3 or more days before surgery.

               -  History (including family history) or symptoms of a congenital or acquired
                  bleeding disorder or vascular malformation; or a history of intracranial,
                  retroperitoneal, or intraocular bleeding within the last 6 months; or is felt to
                  be at high risk for bleeding for other reasons.

               -  Gastrointestinal bleeding within 90 days before surgery or endoscopically
                  verified ulcer disease within 30 days before surgery.

               -  Indwelling intrathecal or epidural catheter during the prophylaxis period (except
                  for epidural catheter if removed after surgery); or unusual difficulty in
                  administering spinal or epidural anesthesia (eg, 3 or more attempts, "traumatic
                  taps").

               -  Major surgery, ischemic stroke, or myocardial infarction within 3 months before
                  Screening.

               -  Uncontrolled hypertension defined as systolic blood pressure (SBP) > 180 mmHg or
                  diastolic blood pressure (DBP) >105 mmHg.

               -  Hypotension defined as SBP <95 mmHg.

               -  Evidence at Screening of symptomatic congestive heart failure requiring
                  treatment.

               -  Chronic atrial fibrillation treated with oral anticoagulants, recurrent atrial
                  arrhythmia(s) or a history of recurrent ventricular tachycardia.

        Laboratory and Procedures

        • Evidence at Screening of: platelet count <100,000/mm3 potassium <3.5 mEq/L hemoglobin
        concentration <10 g/dL or hematocrit <30% serum ALT or AST >2 times ULN serum creatinine
        >2.0 mg/dL (180 µm/L)

          -  Contraindication to venography, including to iodinated contrast medium

          -  QTc on Screening ECG >450 msec and/or a personal or family history of "Long QT
             Syndrome".

        Medications

          -  Contraindication to anticoagulation for VTE prophylaxis, including a contraindication
             to receiving heparin or heparinoids.

          -  Administration of the following drugs within 7 days before TKR: thrombolytic agents,
             anticoagulants and/or anti-platelet agents (eg, heparins, warfarin, dipyridamole,
             sulfinpyrazone, ticlopidine, dextran, clopidogrel). Aspirin up to 325 mg once daily
             and NSAIDs are allowed but discouraged.

          -  Use of class III antiarrhythmics drugs (eg, dofetilide, ibutilide, amiodarone,
             bretylium, sotalol) within 30 days prior to TKR.

        General

          -  Participation in any investigational drug study 30 days prior to enrollment is
             prohibited. Participation in a device trial prior to enrollment is acceptable.

          -  Any condition which could interfere with or for which the treatment of might interfere
             with the conduct of the study, or which would, in the opinion of the Investigator,
             unacceptably increase the risk of the subject's participation in the study. This would
             include, but is not limited to alcoholism, drug dependency or abuse, psychiatric
             disease, epilepsy or any unexplained blackouts.