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

Septic Shock Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03901807
• Other study ID #: SDI-PMX-NA003
• Status: Recruiting
• Phase: N/A
• Start date: October 17, 2019
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2023
• Source: Spectral Diagnostics (US) Inc.
• Contact: Debra Foster
• Phone: 416-626-3233
• Email: dfoster[@]spectraldx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endotoxemia
• Septic Shock
• Shock
• Shock, Septic

Intervention

Device:
• 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).

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Pulmonary Associates	Boulder	Colorado
United States	Cooper Health System	Camden	New Jersey
United States	Medical University of South Carolina	Charleston	South Carolina
United States	CHI Memorial	Chattanooga	Tennessee
United States	Parkridge Hospital	Chattanooga	Tennessee
United States	Cleveland Clinic	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	West Virginia University	Morgantown	West Virginia
United States	Mt Sinai Hospital	New York	New York
United States	Stanford University	Palo Alto	California
United States	UPMC	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	University of California, San Francisco	San Francisco	California
United States	Louisiana State University Health Shreveport	Shreveport	Louisiana
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Stony Brook University	Stony Brook	New York
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Spectral Diagnostics (US) Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	MAP comparison	compare changes in mean arterial blood pressure (MAP) from Day 0 to Day 3 in each group	3 days
Secondary	Vasopressor dose comparison	compare the changes in vasopressor doses from Day 0 to Day 3 in each group	3 days
Secondary	Survival time comparison	compare the survival time from baseline to death within 28 days in each group	28 days
Secondary	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	28 days
Secondary	Day 14 mortality comparison	compare mortality at 14 days post baseline in each group	14 days
Secondary	Vasopressor use comparison	compare total duration of vasopressor use from Day 0 to Day 3 in each group	3 days