Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Endotoxemic Septic Shock in a Randomized, Open-Label Study

Inclusion Criteria:

   1. Age ≥18 years of age

   2. Hypotension requiring vasopressor support: Requirement for at least one of the
   vasopressors listed below, at the dose shown below, for at least 2 continuous hours
   and no more than 30 hours

      1. Norepinephrine > 0.05mcg/kg/min

      2. Dopamine > 10 mcg/kg/min

      3. Phenylephrine > 0.4 mcg/kg/min

      4. Epinephrine > 0.05 mcg/kg/min

      5. Vasopressin > 0.03 units/min

      6. Vasopressin (any dose) in combination with another vasopressor listed above

   3. The subject must have received intravenous fluid resuscitation of a minimum of 30mL/kg
   administered within 24 hours of eligibility

   4. Documented or suspected infection defined as definitive or empiric intravenous
   antibiotic administration

   5. The subject must have a screening multi-organ dysfunction score (MODS) >9 OR a
   sequential organ failure assessment (SOFA) >11, in the event a complete MODS cannot be
   obtained due to missing measurements

   6. Endotoxin Activity Assay between ≥ 0.60 to <0.90 EA units

   7. Evidence of at least 1 of the following criteria for new onset organ dysfunction that
   is considered to be due to the acute illness:

      1. Requirement for positive pressure ventilation via an endotracheal tube or
      tracheostomy tube

      2. Thrombocytopenia defined as acute onset of platelet count <150,000µ/L or a
      reduction of 50% from prior known levels

      3. Acute oliguria defined as urine output <0.5mL/kg/hr for at least 6 hours despite
      adequate fluid resuscitation

Exclusion Criteria:

   1. Inability to obtain an informed consent from the subject, family member or an
   authorized surrogate

   2. Lack of commitment for full medical support

   3. Inability to achieve or maintain a minimum mean arterial pressure (MAP) of ≥ 65mmHg
   despite vasopressor therapy and fluid resuscitation

   4. Subject has end-stage renal disease and requires chronic dialysis

   5. There is clinical support for non-septic shock such as:

      1. Acute pulmonary embolus

      2. Transfusion reaction

      3. Severe congestive heart failure (e.g. NYHA Class IV, ejection fraction < 35%)

   6. Subject has had chest compressions as part of CPR during this hospitalization without
   immediate return to communicative state

   7. Subject has had an acute myocardial infarction (AMI) within the past 4 weeks

   8. Subject has uncontrolled hemorrhage (acute blood loss requiring > 3 UPC in the past 24
   hours)

   9. Major trauma within 36 hours of screening

10. Subject has severe granulocytopenia (leukocyte count less than 500 cells/mm3) or
   severe thrombocytopenia (platelet count less than 30,000 cells/mm3)

11. HIV infection in association with a last known or suspected CD4 count of <50/mm3

12. Subject's baseline state is non-communicative

13. Subject has sustained extensive third-degree burns within the past 7 days

14. Body weight < 35 kg (77 pounds)

15. Known hypersensitivity to Polymyxin B

16. Subject has known sensitivity or allergy to heparin or has a history of heparin
   associated thrombocytopenia (H.I.T.)

17. Subject is currently enrolled in an investigational drug or device trial

18. Subject has been previously enrolled in the current trial

19. Any other condition, that in the opinion of the investigator, would preclude the
   subject from being a suitable candidate for enrollment, such as end-stage chronic
   illness (eg. lack of source control and bowel necrosis) with no reasonable expectation
   of survival to hospital discharge