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

Primary Purpose

Septic Shock, Endotoxemia

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge
Sponsored by
Spectral Diagnostics (US) Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring sepsis, septic shock, severe sepsis, endotoxemia, endotoxemic, TIGRIS, PMX, Toraymyxin, EAA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • University of Arkansas for Medical SciencesRecruiting
  • Stanford University
  • University of California, San FranciscoRecruiting
  • Pulmonary AssociatesRecruiting
  • George Washington UniversityRecruiting
  • Louisiana State University Health ShreveportRecruiting
  • Baystate Medical CenterRecruiting
  • University of MichiganRecruiting
  • Henry Ford Hospital
  • Washington University
  • Cooper Health System
  • Mt Sinai HospitalRecruiting
  • Stony Brook UniversityRecruiting
  • Cleveland ClinicRecruiting
  • UPMCRecruiting
  • Medical University of South CarolinaRecruiting
  • CHI MemorialRecruiting
  • Parkridge HospitalRecruiting
  • West Virginia UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

PMX Treatment

Control

Arm Description

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

Standard medical care alone

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
April 2, 2019
Last Updated
June 8, 2023
Sponsor
Spectral Diagnostics (US) Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03901807
Brief Title
Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Endotoxemic Septic Shock in a Randomized, Open-Label Study
Acronym
TIGRIS
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 17, 2019 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spectral Diagnostics (US) Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock, Endotoxemia
Keywords
sepsis, septic shock, severe sepsis, endotoxemia, endotoxemic, TIGRIS, PMX, Toraymyxin, EAA

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PMX Treatment
Arm Type
Experimental
Arm Description
Standard medical care for septic shock plus treatment with the PMX cartridge (twice approximately 24 hours apart)
Arm Title
Control
Arm Type
No Intervention
Arm Description
Standard medical care alone
Intervention Type
Device
Intervention Name(s)
Toraymyxin PMX 20R Extracorporeal Hemoperfusion Cartridge
Intervention 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).
Primary Outcome Measure Information:
Title
Day 28 mortality comparison
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
MAP comparison
Description
compare changes in mean arterial blood pressure (MAP) from Day 0 to Day 3 in each group
Time Frame
3 days
Title
Vasopressor dose comparison
Description
compare the changes in vasopressor doses from Day 0 to Day 3 in each group
Time Frame
3 days
Title
Survival time comparison
Description
compare the survival time from baseline to death within 28 days in each group
Time Frame
28 days
Title
Day 28 mortality comparison for patients on norepinephrine >0.1 mcg/kg/min
Description
compare mortality at 28 days post baseline for patients with baseline norepinephrine dose >0.1 mcg/kg/min in each group
Time Frame
28 days
Title
Day 14 mortality comparison
Description
compare mortality at 14 days post baseline in each group
Time Frame
14 days
Title
Vasopressor use comparison
Description
compare total duration of vasopressor use from Day 0 to Day 3 in each group
Time Frame
3 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Acute oliguria defined as urine output <0.5mL/kg/hr for at least 6 hours despite adequate fluid resuscitation Exclusion Criteria: 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 Subject has sustained extensive third-degree burns within the past 7 days Body weight < 35 kg (77 pounds) Known hypersensitivity to Polymyxin B Subject has known sensitivity or allergy to heparin or has a history of heparin associated thrombocytopenia (H.I.T.) Subject is currently enrolled in an investigational drug or device trial Subject has been previously enrolled in the current trial 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Debra Foster
Phone
416-626-3233
Ext
2001
Email
dfoster@spectraldx.com
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-0111
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Name
Pulmonary Associates
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Individual Site Status
Recruiting
Facility Name
George Washington University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Individual Site Status
Recruiting
Facility Name
Louisiana State University Health Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Individual Site Status
Recruiting
Facility Name
Baystate Medical Center
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Withdrawn
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Withdrawn
Facility Name
Cooper Health System
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Individual Site Status
Terminated
Facility Name
Mt Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Stony Brook University
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Individual Site Status
Recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Name
CHI Memorial
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Individual Site Status
Recruiting
Facility Name
Parkridge Hospital
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Individual Site Status
Recruiting
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26505
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There are no plans for sharing IPD at this time.

Learn more about this trial

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

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