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

NCT03901807 | Active Not Recruiting DMC FDA Device

• 1 other identifier: SDI-PMX-NA003
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 20

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

Conditions

Septic Shock; Endotoxemia

Keywords

sepsis; septic shock; severe sepsis; endotoxemia; endotoxemic; TIGRIS; PMX; Toraymyxin; EAA; Spectral Medical

Outcome Measures

Primary Outcomes (1)

• Day 28 mortality comparison

  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.

  28 days

Secondary Outcomes (8)

• Day 90 mortality comparison

  90 days

• MAP comparison

  3 days

• Vasopressor dose comparison

  3 days

• Survival time comparison

  28 days

• Day 28 mortality comparison for patients on norepinephrine >0.1 mcg/kg/min

  28 days

Study Arms (2)

PMX Treatment

EXPERIMENTAL

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

Device: Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge

Control

NO INTERVENTION

Standard medical care alone

Interventions

Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge 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).

PMX Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years of age
• 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
• The subject must have received intravenous fluid resuscitation of a minimum of 30mL/kg administered within 24 hours of eligibility
• Documented or suspected infection defined as definitive or empiric intravenous antibiotic administration
• 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
• Endotoxin Activity Assay between ≥ 0.60 to \<0.90 EA units
• 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

You may not qualify if:

• Inability to obtain an informed consent from the subject, family member or an authorized surrogate
• Lack of commitment for full medical support
• Inability to achieve or maintain a minimum mean arterial pressure (MAP) of ≥ 65mmHg despite vasopressor therapy and fluid resuscitation
• Subject has end-stage renal disease and requires chronic dialysis
• 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%)
• Subject has had chest compressions as part of CPR during this hospitalization without immediate return to communicative state
• Subject has had an acute myocardial infarction (AMI) within the past 4 weeks
• Subject has uncontrolled hemorrhage (acute blood loss requiring \> 3 UPC in the past 24 hours)
• Major trauma within 36 hours of screening
• Subject has severe granulocytopenia (leukocyte count less than 500 cells/mm3) or severe thrombocytopenia (platelet count less than 30,000 cells/mm3)
• HIV infection in association with a last known or suspected CD4 count of \<50/mm3
• Subject's baseline state is non-communicative

Sponsors & Collaborators

• Spectral Diagnostics (US) Inc.: lead

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-0111, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Pulmonary Associates

Boulder, Colorado, 80909, United States

Location

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Louisiana State University Health Shreveport

Shreveport, Louisiana, 71103, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Cooper Health System

Camden, New Jersey, 08103, United States

Location

Rutgers, The State University of New Jersey

Piscataway, New Jersey, 08854, United States

Location

Mt Sinai Hospital

New York, New York, 10029, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

CHI Memorial

Chattanooga, Tennessee, 37404, United States

Location

Parkridge Hospital

Chattanooga, Tennessee, 37404, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Institute for Extracorporeal Life Support

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Neyra JA, Legrand M, Tidswell MA, Al-Khafaji A, Galphin C, Rains R, Davison D, Tolwani A, Chen JT, Bender WS, Busse LW, Meena NK, DellaVolpe J, Williams GW, Kashani KB, Gunnerson KJ, McMahon BA, Eaton J, Khan S, Kohli-Seth R, Jagpal S, Klein D, Kamaluddin E, Foster DM, Walker PM, Tomlinson G, Kellum JA. Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised, controlled, phase 3 trial. Lancet Respir Med. 2026 Mar 23:S2213-2600(26)00047-0. doi: 10.1016/S2213-2600(26)00047-0. Online ahead of print.

  PMID: 41887242 DERIVED

• 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.

  PMID: 38214917 DERIVED

MeSH Terms

Conditions

Shock, Septic; Endotoxemia; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Bacteremia; Toxemia

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The subjects will be randomized in a 2:1 ratio to the two groups (PMX cartridge plus standard of care: standard of care alone). A blocked randomization scheme will be used to provide approximately balanced ratio allocations to the two groups for each investigative site during the study.

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 3, 2019
• Study Start: January 9, 2020
• Primary Completion: May 8, 2025
• Study Completion: April 30, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)