Septic Shock
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DEVICEAlteco LPS Adsorber
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.
DEVICEPlacebo
Exactly the same as Alteco LPS Adsorber but no peptide component has been attached to the matrix (i.e. there is no adsorber functionality)
Sponsors
TFS Trial Form Support
Uppsala University
Alteco Medical AB
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
Illness severity criteria: At enrolment subjects must meet inclusion criteria #1 through #3 listed below to be eligible to enter the clinical investigation: 1. Subjects must have suspected severe infection of abdominal or urogenital origin for which the subject is receiving intravenous antimicrobial therapy as the main reason for organ support 2. Subjects, males or females, must be 18 years or older. 3. Subjects or legally acceptable representatives, as appropriate, are willing and able to provide signed informed consent. Treatment criteria: Prior to randomization, subjects must meet all inclusion criteria (#4 through #7) listed below to be assigned to a treatment group: 4. Appropriate vascular access must have been obtained. 5. Subjects must have received ≥ 30 mL/kg of intravenous fluid within the six (6) hours prior to randomization. 6. Subjects must have plasma/serum lactate \>2 mmol/L despite adequate resuscitation AND a continuous requirement for vasopressor support 7. Subjects must be able to initiate the clinical investigation intervention within 12 hours of fulfilment of the illness severity criteria.
Exclusion criteria
1. Subjects who meet any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Characterization of all reported USADEs and ASADEs. | 6-28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative change from baseline in SOFA score | 6-28 days | — |
| Relative change from baseline in renal function | 6-28 days | Renal function is assessed by: S-creatinine, P-Cystatin C, P-Urea, eGFR, KDIGO stage, Fluid balance, and Daily urinary output |
| Relative change from baseline in liver function | 6-28 days | Liver function is assessed by: Prothrombin complex INR, P-Albumin, and P-Bilirubin |
| Relative change from baseline in circulatory support | 6-28 days | Circulatory support is assessed by: Vasopressor load, Inotropic score, MAP, Vasopressor dependence index, P-Lactate, Blood gas, and Vasopressor-free days. |
| Relative change from baseline in respiratory support | 6-28 days | 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 |
| Relative change from baseline in ICU mortality | 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. | 2 days | — |
| Clinical outcome during stay at Hospital following ICU-discharge of the total extension of renal support | 6-28 days | — |
| Clinical outcome during stay at Hospital following ICU-discharge of 28-day mortality | 6-28 days | — |
| Clinical outcome during stay at Hospital following ICU-discharge of hospital length of stay up to 28 days | 6-28 days | — |
| Levels of inflammatory response biomarkers | 6-28 days | — |
| Determination of the molecular components extracted from blood circulation and captured in Alteco® LPS Adsorber. | 6-28 days | This is an exploratory outcome, there will be a screening of which molecules that have been captured. |
| Characterization of all reported AEs (regardless of attribution), ADEs, and device deficiencies | 6-28 days | — |
| Relative change from baseline in ICU length of stay | 6-28 days | — |
Countries
Finland, Norway, Sweden
Outcome results
None listed