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

NCT ID: NCT03901807

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-09
• Study Completion Date: 2026-04-30

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.

Conditions

Septic Shock; Endotoxemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PMX Treatment

Standard medical care for septic shock plus treatment with the PMX cartridge (twice approximately 24 hours apart)

Group Type: EXPERIMENTAL

Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge

Intervention Type: DEVICE

TORAYMYXIN PMX-20R (PMX) is an extracorporeal hemoperfusion cartridge intended for the selective removal of endotoxin from circulating blood through direct hemoperfusion (DHP). Each treatment will target 2 hours with a minimum of 1 ½ hours, at a flow rate of approximately 100 mL/minute, (range of 80 to 120 mL/minute).

Control

Standard medical care alone

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge

TORAYMYXIN PMX-20R (PMX) is an extracorporeal hemoperfusion cartridge intended for the selective removal of endotoxin from circulating blood through direct hemoperfusion (DHP). Each treatment will target 2 hours with a minimum of 1 ½ hours, at a flow rate of approximately 100 mL/minute, (range of 80 to 120 mL/minute).

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spectral Diagnostics (US) Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California, San Francisco

San Francisco, California, United States

Pulmonary Associates

Boulder, Colorado, United States

George Washington University

Washington D.C., 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

Mayo Clinic

Rochester, Minnesota, 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

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

Countries

United States

References

Bellomo R, Mehta RL, Forni LG, Zarbock A, Ostermann M, Ronco C; Acute Disease Quality Initiative Hemoadsorption Working Group. Hemoadsorption. Clin J Am Soc Nephrol. 2024 Jan 12;19(6):803-806. doi: 10.2215/CJN.0000000000000433. Epub 2024 Jan 12. No abstract available.

Reference Type: DERIVED

PMID: 38214917 (View on PubMed)

Other Identifiers

SDI-PMX-NA003

Identifier Type: -

Identifier Source: org_study_id