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

Overview

About this study

The purpose of this study is to compare the safety and effectiveness of the PMX cartridge (Toraymyxin) based on mortality at 28 days in patients with septic shock and endotoxemia who are treated with standard medical care plus the use of the PMX cartridge, versus patients who receive standard medical care alone.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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:

  • Norepinephrine > 0.05mcg/kg/min.;
  • Dopamine > 10 mcg/kg/min.;
  • Phenylephrine > 0.4 mcg/kg/min.;
  • Epinephrine > 0.05 mcg/kg/min.;
  • Vasopressin > 0.03 units/min.;
  • 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:

  • Requirement for positive pressure ventilation via an endotracheal tube or tracheostomy tube;
  • Thrombocytopenia defined as acute onset of platelet count < 150,000µ/L or a reduction of 50% from prior known levels;
  • 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:

  • Acute pulmonary embolus;
  • Transfusion reaction;
  • 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/mm^3).

11. HIV infection in association with a last known or suspected CD4 count of < 50/mm^3.

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 (e.g., lack of source control and bowel necrosis) with no reasonable expectation
of survival to hospital discharge.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/3/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Kianoush Banaei Kashani, M.D., M.S.

Open for enrollment

Contact information:

Ryan Helland

(507) 422-3998

Helland.Ryan@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20551470

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