Clinical trial NCT03901807: Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Endotoxemic Septic Shock in a Randomized, Open-Label Study
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Septic Shock
Endotoxemia
Keywords: sepsis
septic shock
severe sepsis
endotoxemia
endotoxemic
TIGRIS
PMX
Toraymyxin
EAA
Spectral Medical
Lead sponsor: Spectral Diagnostics (US) Inc.
Sponsor class: INDUSTRY
First posted: 2019-04-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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

Primary outcomes:
measure: Day 28 mortality comparison
timeFrame: 28 days
Secondary outcomes:
measure: Day 90 mortality comparison
timeFrame: 90 days
measure: MAP comparison
timeFrame: 3 days
measure: Vasopressor dose comparison
timeFrame: 3 days
measure: Survival time comparison
timeFrame: 28 days
measure: Day 28 mortality comparison for patients on norepinephrine >0.1 mcg/kg/min
timeFrame: 28 days
measure: Day 14 mortality comparison
timeFrame: 14 days
measure: Vasopressor use comparison
timeFrame: 3 days
measure: 12 month mortality comparison
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boulder
country: United States
facility: Pulmonary Associates
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Shreveport
country: United States
facility: Louisiana State University Health Shreveport
state: Louisiana
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Camden
country: United States
facility: Cooper Health System
state: New Jersey
city: Piscataway
country: United States
facility: Rutgers, The State University of New Jersey
state: New Jersey
city: New York
country: United States
facility: Mt Sinai Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: CHI Memorial
state: Tennessee
city: Chattanooga
country: United States
facility: Parkridge Hospital
state: Tennessee
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: Institute for Extracorporeal Life Support
state: Texas
Study officials:
References: