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

Not Applicable

Recruiting

• Conditions: Endotoxemia; Septic Shock
• Interventions: Device: Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge

• Registration Number: NCT03901807
• Lead Sponsor: Spectral Diagnostics (US) Inc.

Brief Summary

Prospective, multicenter, randomized, open-label study of standard of care plus the PMX cartridge versus standard of care alone in patients with endotoxemic septic shock

Detailed Description

This is a prospective, multicenter, randomized, open-label trial of standard medical care plus the PMX cartridge versus standard medical care alone, in subjects with endotoxemia and septic shock. Subjects in critical care areas will be assessed for septic shock using known or suspected infection, multiple organ failure, fluid resuscitation and hypotension requiring vasopressor support as primary criteria. Subjects will meet all entry criteria for study if endotoxin activity is within the range of ≥ 0.60 to \<0.90.

Eligible and consented subjects will be randomized to receive either the PMX cartridge (administered twice for 1½ to 2 hours per treatment session approximately 24 hours apart) plus standard medical care or standard medical care alone. For all randomized subjects, a follow-up visit (if they are still in the hospital) or a telephone call will be completed at Day 28 (or later) to determine their mortality status. In surviving subjects, a follow-up visit or telephone call to determine their mortality status will also take place at approximately three months (i.e. Day 90) and 12 months after the subject was randomized.

Study Timeline

• Study First Submitted: 2019-04-02
• Study First Submitted QC: 2019-04-02
• Study First Posted: 2019-04-03
• Study Start: 2020-01-09
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Primary Completion: 2025-04-30
• Study Completion: 2026-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PMX Treatment	Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge	Standard medical care for septic shock plus treatment with the PMX cartridge (twice approximately 24 hours apart)

Primary Outcome Measures

Name	Time	Method
Day 28 mortality comparison	28 days	The primary objective is to compare the safety and efficacy 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.

Secondary Outcome Measures

Name	Time	Method
Survival time comparison	90 days	compare the survival time from baseline to death within 90 days in each group
MAP comparison	3 days	compare changes in mean arterial blood pressure (MAP) from Day 0 to Day 3 in each group
Vasopressor use comparison	3 days	compare total duration of vasopressor use from Day 0 to Day 3 in each group
Day 90 and Day 12 mortality comparison	90 Days and 12 Months	compare mortality at 90 days and 12 months post baseline in each group
Vasopressor dose comparison	3 days	compare the changes in vasopressor doses from Day 0 to Day 3 in each group
Day 28 mortality comparison for patients on norepinephrine >0.1 mcg/kg/min	28 days	compare mortality at 28 days post baseline for patients with baseline norepinephrine dose \>0.1 mcg/kg/min in each group
Day 14 mortality comparison	14 days	compare mortality at 14 days post baseline in each group

Trial Locations

Locations (29)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Pulmonary Associates; 🇺🇸 Boulder, Colorado, United States

George Washington University; 🇺🇸 Washington, District of Columbia, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Louisiana State University Health Shreveport; 🇺🇸 Shreveport, Louisiana, United States

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Cooper Health System; 🇺🇸 Camden, New Jersey, United States

Rutgers, The State University of New Jersey; 🇺🇸 Piscataway, New Jersey, United States

Mt Sinai Hospital; 🇺🇸 New York, New York, United States

Stony Brook University; 🇺🇸 Stony Brook, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

CHI Memorial; 🇺🇸 Chattanooga, Tennessee, United States

Parkridge Hospital; 🇺🇸 Chattanooga, Tennessee, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

Institute for Extracorporeal Life Support; 🇺🇸 San Antonio, Texas, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

West Virginia University; 🇺🇸 Morgantown, West Virginia, United States

Aurora St. Luke's Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States