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.