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

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