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

A Prospective, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of PMX Cartridge in Addition to Standard Medical Care for Patients With Endotoxemic Septic Shock

Sponsors

Lead Sponsor: Spectral Diagnostics (US) Inc.

Source 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.

Overall Status Recruiting
Start Date 2019-10-17
Completion Date 2022-09-30
Primary Completion Date 2021-10-31
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Day 28 mortality comparison 28 days
Secondary Outcome
Measure Time Frame
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
Day 14 mortality comparison 14 days
Vasopressor use comparison 3 days
Enrollment 150
Condition
Intervention

Intervention Type: Device

Intervention Name: Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge

Description: 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).

Arm Group Label: PMX Treatment

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 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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Contact

Last Name: Debra Foster

Phone: 416-626-3233

Phone Ext.: 2001

Email: [email protected]

Location
Facility: Status:
Stanford University | Palo Alto, California, 94305, United States Recruiting
Pulmonary Associates | Boulder, Colorado, 80909, United States Not yet recruiting
George Washington University | Washington, District of Columbia, 20037, United States Recruiting
Baystate Medical Center | Springfield, Massachusetts, 01199, United States Recruiting
Henry Ford Hospital | Detroit, Michigan, 48202, United States Recruiting
Washington University | Saint Louis, Missouri, 63130, United States Recruiting
Cooper Health System | Camden, New Jersey, 08103, United States Recruiting
Mt Sinai Hospital | New York, New York, 10029, United States Recruiting
Stony Brook University | Stony Brook, New York, 11794, United States Recruiting
UPMC | Pittsburgh, Pennsylvania, 15213, United States Recruiting
CHI Memorial | Chattanooga, Tennessee, 37404, United States Recruiting
Parkridge Hospital | Chattanooga, Tennessee, 37404, United States Recruiting
Location Countries

United States

Verification Date

2020-11-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access Yes
Condition Browse
Number Of Arms 2
Arm Group

Label: PMX Treatment

Type: Experimental

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

Label: Control

Type: No Intervention

Description: Standard medical care alone

Acronym TIGRIS
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: 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.

Primary Purpose: Treatment

Masking: None (Open Label)

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