A Safety and Efficacy Study of Intravenous E5564 in Patients With Severe Sepsis

Inclusion Criteria:

• Presently admitted, or about to be transferred, to the ICU.
• Women of Child-bearing potential must have a negative serum (or urine) hCG assay within 24 hours prior to drug administration.
• Any Race.
• Severe Sepsis [newly developed respiratory failure, refractory shock, renal dysfunction, hepatic dysfunction, or metabolic acidosis and at least three signs of SIRS (systematic inflammatory response syndrome)].
• Objective signs of infection likely to be caused by a bacterial or fungal pathogen.
• Patients must receive study medication within 8 to 12 hours of recognition of the initial sepsis-related organ failure.
• APACHE Predicted risk of mortality score between 20% and 80%.
• An intent by physicians and family to aggressively treat the patient for the 28 day study period.

Exclusion Criteria:

• Cardiogenic or hypovolemic shock.
• Acute third degree burns involving >20% of body surface.
• Recipients of non-autologous organ transplants within the past year.
• Pregnancy.
• Chronic vegetative state.
• Uncontrolled serious hemorrhage (.2 units of blood/platelets in the previous 24 hours). Patients may be considered for enrollment if bleeding has stopped and patients are still otherwise qualified.
• Unwilling or unable to be fully evaluated for all follow-up visits.
• Patients who are classified as "Do not resusitate" or "Do not treat."
• Patients who develop severe sepsis <36 hours post trauma or post-surgery. Patients may be considered for enrollment >36 hours post-trauma or post-surgery, if they meet other inclusion criteria.
• Patients with a predicted risk of mortality score of <20% or >80% after recognition of qualifying organ failure.
• Patients with a predicted risk of mortality of <51% for whom Xigris® use is planned.