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 thevasopressors listed below, at the dose shown below, for at least 2 continuous hoursand no more than 30 hours

3. Norepinephrine > 0.05mcg/kg/min

4. Dopamine > 10 mcg/kg/min

5. Phenylephrine > 0.4 mcg/kg/min

6. Epinephrine > 0.05 mcg/kg/min

7. Vasopressin > 0.03 units/min

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

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

10. Documented or suspected infection defined as definitive or empiric intravenousantibiotic administration

11. The subject must have a screening multi-organ dysfunction score (MODS) >9 OR asequential organ failure assessment (SOFA) >11, in the event a complete MODS cannotbe obtained due to missing measurements

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

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

14. Requirement for positive pressure ventilation via an endotracheal tube ortracheostomy tube

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

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

Exclusion Criteria:

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

2. Lack of commitment for full medical support

3. Inability to achieve or maintain a minimum mean arterial pressure (MAP) of ≥ 65mmHgdespite 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:

6. Acute pulmonary embolus

7. Transfusion reaction

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

9. Subject has had chest compressions as part of CPR during this hospitalizationwithout immediate return to communicative state

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

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

12. Major trauma within 36 hours of screening

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

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

15. Subject's baseline state is non-communicative

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

17. Body weight < 35 kg (77 pounds)

18. Known hypersensitivity to Polymyxin B

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

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

21. Subject has been previously enrolled in the current trial

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