Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy

Inclusion Criteria: * Subject must be receiving treatment in an ICU, or in an acute care setting (e.g., ER, RR) * Clinical objective evidence of bacterial infection and a known site of infection. * Cardiovascular dysfunction or Respiratory Failure due to sepsis. * Coagulopathy characterized by an INR \>1.40 without other known causes. Exclusion Criteria: * Subject or Authorized Representative is unable to provide informed consent. * Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of enrolling into the study. * Subject is of childbearing potential and does not have a negative pregnancy test. * Subject is \< 18 years of age. * Subject has a known allergy to ART-123 or any components of the drug product. * Subject is unwilling to allow transfusion of blood or blood products. * Subject has an advance directive to withhold life-sustaining treatment. * Subject has had previous treatment with ART-123. * Body weight ≥ 175 kg. * Platelets \< 30,000/ mm3 for any reason, PT prolongation or thrombocytopenia that is not due to sepsis. * Any surgery that is potentially hemorrhagic (e.g. intra-thoracic, intra-abdominal or non-traumatic orthopedic surgery of the femur or pelvis) that is completed within 12 hours prior to first dose of study drug, or ongoing impairment of hemostasis as a result of one of these procedures * History of head trauma, spinal trauma, or other acute trauma with an increased risk of bleeding within 3 months prior to consent. * Cerebral Vascular Accident (CVA) within 3 months prior to consent. * Any history of intracerebral arteriovenous malformation (AVM), cerebral aneurysm, or mass lesions of the central nervous system. * History of congenital bleeding diathesesor anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia). * Significant gastrointestinal bleeding within 6 weeks prior to consent. * Subject is diagnosed with a known medical condition associated with a hypercoagulable state. * Child-Pugh score of 10-15 (Class C) * Portosystemic hypertension or known history of bleeding esophageal varices. * History of solid organ, allogeneic bone marrow, or stem cell transplantation within the 6 months prior to consent. * Acute pancreatitis where infection has not been documented by a positive blood or abdominal fluid culture or gram stain consistent with bacterial infection. * Subjects with renal dysfunction defined as (a) Chronic renal failure requiring renal replacement therapy (RRT), or (b) Acute renal failure with onset of oliguria (urine output \< 0.3 ml/kg/hr) \> 48 hours prior to first dose of study drug whether receiving RRT or not * Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 72 hours prior to first does of study drug. * Life expectancy \< 90 days. * Current use of any chemotherapy agent likely to cause myeloablation (severe or complete depletion of bone marrow). * Participation in another research study involving an investigational agent within 30 days prior to consent or projected study participation during the 28 days post study randomization. * Confirmed or suspected endocarditis