Safety and Efficacy Study of ART-123 in the Treatment of Severe Sepsis With Coagulopathy

Inclusion Criteria:

• Subject must be receiving treatment in an ICU, or in an acute care setting with orders to transfer to ICU.
• Clinical 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.
• PT prolongation or thrombocytopenia that is not due to sepsis.
• Intra-thoracic or intra-abdominal surgery within 12 hours prior to consent, or ongoing bleeding issues 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 diatheses.
• 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.
• Severe renal failure requiring chronic or acute need of hemodialysis, hemofiltration or peritoneal dialysis.
• Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 72 hours prior to consent.
• 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.