['end-stage renal disease (esrd)']
['isis 416858', 'placebo']

        Inclusion Criteria:

          -  End stage renal disease maintained on outpatient hemodialysis at a healthcare center
             for > 3 months from screening with hemodialysis using heparin (unfractionated heparin
             or low-molecular weight heparin) 3 times per week for a minimum of 3 hours per
             dialysis session and plan to continue this throughout the study.

        Exclusion Criteria:

          -  Documented thrombotic event (acute coronary syndrome, stroke or transient ischemic
             attack, venous thromboembolic event) in the past 3 months.

          -  Active bleeding within the past 3 months from screening or documented bleeding
             diathesis (history of bleeding disorder) or Screening values of:

               -  Platelet count < 150,000 cells/mm3

               -  INR > 1.4

               -  aPTT > upper limit of normal (ULN)

          -  Abnormal liver function at Screening:

               -  ALT or AST > 2 x ULN

               -  Total bilirubin > ULN

          -  Concomitant medication restrictions: Concomitant use of anticoagulant/antiplatelet
             agents (e.g., dabigatran, rivaroxaban, clopidogrel) that may affect coagulation
             (except low dose aspirin (≤ 100 mg/day) during Treatment and Post-treatment Evaluation
             Periods is not allowed.

          -  Uncontrolled hypertension as judged by the Investigator. Patients with a pre- or
             post-dialysis blood pressure (BP) that is > 160 mmHg on at least 3 of last 5 dialysis
             treatments.

          -  Planned major surgery in the next 6 months (e.g. renal transplant surgery)
      