The primary objective of this clinical investigation is to investigate the feasibility and possible benefits of the Alteco® LPS Adsorber in treating patients with septic shock with presumed endotoxemia of abdominal or urogenital origin.
OVERALL CLINICAL INVESTIGATION DESIGN: This is a multicentre, stratified, parallel, double-blinded, randomized, feasibility clinical investigation of the Alteco® LPS Adsorber. Subjects will be enrolled in an adaptive fashion with up to two interim analyses, and the possibility of recruiting additional patients, in order to establish an indication of the feasibility of treating a target population of subjects with septic shock and endotoxemia. Subjects will be stratified in accordance with the origin of their infection, i.e. abdominal or urogenital sepsis. Subjects in each stratum will receive either: * LPS Adsorber group (i.e. investigational medical device \[IMD\] group): current best practice in combination with Alteco® LPS Adsorber treatment, OR * Placebo device group (i.e. comparator group): current best practice in combination with placebo adsorber treatment. Allocation to either treatment arm will be performed in a 1:1 ratio. Upon enrolment (i.e. pre-treatment phase), subjects admitted to the ICU with suspected endotoxemia will be screened for fulfilment of the "Illness Severity Criteria" confirming early stage severe sepsis. Within six (6) hours of enrolment, subjects who also fulfil the "Treatment Criteria" confirming septic shock will be eligible for randomization. Randomization to either of the treatment groups will be performed as close as possible to start of treatment with the Alteco® LPS Adsorber or placebo device. Treatment with LPS Adsorber or placebo device must be initiated within six (6) hours (Day 1) following fulfilment of the "Treatment Criteria". A second device treatment will be performed 24 hours after the end of the first device treatment on Day 2, as long there is no evidence that treatment with the investigational device will not be beneficial or will indicate an unnecessary risk for subjects (for example, the subject is vasopressor support-free). Initially: 20 abdominal sepsis subjects (Stratum A) and 12 urogenital sepsis subjects (Stratum B) Optional: additional 12 subjects (abdominal, urogenital or both) after interim analysis decision.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
15
Alteco® LPS Adsorber is a Class IIa medical device developed in accordance with existing international standards. Alteco® LPS Adsorber does not contain any pharmaceutical or toxic components. Alteco® LPS Adsorber is used for the adsorption of LPS as endotoxins. The capturing component is a specially designed synthetic peptide developed for adsorption of endotoxin. The capturing component has high affinity to Lipid A, i.e. a constant component in the endotoxin molecule, which ensures efficient reduction of endotoxins from different bacterial species.
Exactly the same as Alteco LPS Adsorber but no peptide component has been attached to the matrix (i.e. there is no adsorber functionality)
Kuopio University Hospital
Kuopio, Finland
Tampere University Hospital
Tampere, Finland
Haukeland Universitetssykehus
Bergen, Norway
Oslo Universitetssykehus
Oslo, Norway
Characterization of all reported USADEs and ASADEs.
Time frame: 6-28 days
Relative change from baseline in plasma endotoxin (p-endotoxin) levels during (i.e. at 2 hours) and immediately after end (i.e. at 6 hours) of treatment with device, on both Day 1 and Day 2.
Time frame: 2 days
Relative change from baseline in SOFA score
Time frame: 6-28 days
Relative change from baseline in renal function
Renal function is assessed by: S-creatinine, P-Cystatin C, P-Urea, eGFR, KDIGO stage, Fluid balance, and Daily urinary output
Time frame: 6-28 days
Relative change from baseline in liver function
Liver function is assessed by: Prothrombin complex INR, P-Albumin, and P-Bilirubin
Time frame: 6-28 days
Relative change from baseline in circulatory support
Circulatory support is assessed by: Vasopressor load, Inotropic score, MAP, Vasopressor dependence index, P-Lactate, Blood gas, and Vasopressor-free days.
Time frame: 6-28 days
Relative change from baseline in respiratory support
Respiratory support is assessed by: PaO2, FiO2 and PaO2/FiO2 ratio, Positive and expiratory pressure, Peak pressure, Tidal volume and minute volume, Respiratory rate, Pa CO2, Respiratory support need as measured by means of ventilator-free days until day for ICU discharge
Time frame: 6-28 days
Relative change from baseline in ICU mortality
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Linköping University Hospital
Linköping, Sweden
Uppsala University Hospital
Uppsala, Sweden
Time frame: 6-28 days
Relative change from baseline in ICU length of stay
Time frame: 6-28 days
Clinical outcome during stay at Hospital following ICU-discharge of the total extension of renal support
Time frame: 6-28 days
Clinical outcome during stay at Hospital following ICU-discharge of 28-day mortality
Time frame: 6-28 days
Clinical outcome during stay at Hospital following ICU-discharge of hospital length of stay up to 28 days
Time frame: 6-28 days
Levels of inflammatory response biomarkers
Time frame: 6-28 days
Determination of the molecular components extracted from blood circulation and captured in Alteco® LPS Adsorber.
This is an exploratory outcome, there will be a screening of which molecules that have been captured.
Time frame: 6-28 days
Characterization of all reported AEs (regardless of attribution), ADEs, and device deficiencies
Time frame: 6-28 days