Endotoxemia, Septic Shock
Conditions
Brief summary
To compare the safety and efficacy of the PMX cartridge based on mortality at 28-days in subjects with septic shock who have high levels of endotoxin and are treated with standard medical care plus use of the PMX cartridge, versus subjects who receive standard medical care alone.
Interventions
TORAYMYXIN PMX-20R (PMX cartridge), Extracorporeal hemoperfusion device. 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).
OTHERStandard medical care for septic shock
Standard medical care for septic shock
Sponsors
Spectral Diagnostics (US) Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hypotension requiring vasopressor support * The subject must have received intravenous fluid resuscitation * Documented or suspected infection * Endotoxin Activity Assay ≥ 0.60 EAA units * Evidence of at least 1 new onset organ dysfunction
Exclusion criteria
* Inability to achieve or maintain a minimum mean arterial pressure (MAP) of 65mmHg * Subject has end stage renal disease and requires chronic dialysis * There is clinical support for non-septic shock * Subject has had chest compressions as part of CPR * Subject has had an acute myocardial infarction (AMI) * Subject has uncontrolled hemorrhage * Major trauma within 36 hours of screening * Subject has severe granulocytopenia * HIV infection with a last known or suspected CD4 count of \<50/mm3 * Subject has sustained extensive third-degree burns * Body weight \< 35 kg (77 pounds) * Known hypersensitivity to polymyxin B * Subject has known sensitivity or allergy to heparin * Subject has screening MOD score of ≤9
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 28 days | Compare mortality at 28 days in subjects treated with standard medical care plus PMX cartridge, versus subjects who received standard medical care alone |
Countries
Canada, United States
Participant flow
Recruitment details
450 subjects randomized out of 921 clinically eligible subjects in 55 ICUs. First patient screened in Jun 2010, last patient screened in Jun 2016.
Pre-assignment details
The following screened subjects were not randomized: * Subject's EAA \<0.06 EA units * Subject met an exclusion criteria prior to randomization * Informed consent for the treatment phase of the study was not signed or consent withdrawn prior to randomization. Subjects who were randomized but not treated (RNT) were not part of safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Sham Standard medical care for septic shock | 226 |
| Treatment Two (2) PMX cartridges administered approximately 24 hours apart, plus standard medical care for septic shock | 224 |
| Total | 450 |
Baseline characteristics
| Characteristic | Sham | Treatment | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 14.7 | 60.9 years STANDARD_DEVIATION 15.1 | 59.8 years STANDARD_DEVIATION 14.9 |
| Race/Ethnicity, Customized Asian | 9 participants | 3 participants | 12 participants |
| Race/Ethnicity, Customized Black | 13 participants | 22 participants | 35 participants |
| Race/Ethnicity, Customized Caucasian | 187 participants | 183 participants | 370 participants |
| Race/Ethnicity, Customized Hispanic | 12 participants | 10 participants | 22 participants |
| Race/Ethnicity, Customized Other | 5 participants | 6 participants | 11 participants |
| Region of Enrollment Canada | 57 participants | 53 participants | 110 participants |
| Region of Enrollment United States | 169 participants | 171 participants | 340 participants |
| Sex: Female, Male Female | 93 Participants | 84 Participants | 177 Participants |
| Sex: Female, Male Male | 133 Participants | 140 Participants | 273 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 78 / 226 | 84 / 224 |
| other Total, other adverse events | 60 / 220 | 56 / 212 |
| serious Total, serious adverse events | 126 / 220 | 140 / 212 |
Outcome results
Primary
Mortality
Compare mortality at 28 days in subjects treated with standard medical care plus PMX cartridge, versus subjects who received standard medical care alone
Time frame: 28 days
Population: All subjects randomized
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sham | Mortality | 78 Participants |
| Treatment | Mortality | 84 Participants |