Clinical trial NCT03457038: Use of Fc-MBL to Detect and Monitor the Presence of PAMPs During Septic Shock
Official title: Use of Fc Mannose-Binding Lectin to Detect and Monitor the Presence of Pathogen-Associated Molecular Patterns During Septic Shock
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Septic Shock
Keywords: Mannose-Binding Lectin, PAMPs,
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Harvard Medical School (HMS and HSDM)
First posted: 2018-03-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Major patients admitted to the Resuscitation Department of the CHU Toulouse-Rangueil for severe sepsis, or development of sepsis during the stay resuscitation; sepsis defined by a SOFA score ≥ 2
Primary purpose: DIAGNOSTIC

Brief summary: Use Mannose Binding Lectin (MBL) as a biomarker to measure levels of Pathogen- Associated Molecular Patterns (PAMP) during septic shock. This will allow evaluating interest of this biomarker to monitor and manage a septic shock. Consecutive patients admitted for sepsis in Intensive Care Unit Department will be included. This biomarker will be compared to all the parameters monitored usually for these patients in standard care.

Detailed description: Septic shock still represent a major cause of admission in intensive care unit, incidence of severe sepsis is increasing, even in western countries, due to aging populations and comorbidities. Definition of septic shock was revised in 2016 by a task force, which emphasizes the need for future iterations. Indeed, there are no simple clinical or biological criteria ton diagnose septic patients with high risk of shock, or to prognose its severity. C-reactive protein (CRP) and procalcitonin (PCT) are the wider biomarkers used to monitor septic patients. But they do not correlate with sepsis severity and moreover do not distinguish unequivocally between infection and noninfected systemic inflammatory response syndrome (SIRS). Each microorganism has number of PAMPs, cell wall components (lipopolysaccharide endotoxin, peptidoglycan, outer membrane vesicles), flagella, mannan... High levels of these pathogen fragments are released in the bloodstream during sepsis. They trigger release of inflammatory cytokines that drive the sepsis cascade. Mannose binding lectin plays a pivotal role in innate immunity, binding with surface sugars of wide range of pathogens and their fragments. Thus MBL promotes opsonophagocytosis and activates the lectin-complement pathway. Fc-MBL, an engineered version of MBL has been developed to capture microorganism and treat sepsis. An ELISA, using Fc-MBL was developed to measure PAMPs in whole blood during sepsis. This assay will use Fc-MBL ELISA to quantify PAMPs during septic shock, to improve diagnostic and monitoring. But also, identifying patients with high levels of PAMPs for dialysis-like sepsis therapies.

PAMP's level will be compared to clinical, biological, microbiological and therapeutic outcomes. Its sensitivity will be evaluated by its kinetic among a septic shock (defined with Sepsis-3 criteria) and by correlation with CRP (C-Reactive Protein) and PCT (Procalcitonin). Its specificity will be evaluated by comparing its levels during septic and non-septic shocks.

Eligibility criteria: Inclusion Criteria:

* Adult patients
* Hospitalized in Intensive Care Unit for sepsis of any etiology
* Patients with shock criteria: defined by a hypotension, hyperlactatemia, the use of vasopressive drugs.
* Patient affiliated to a social security scheme- Patient giving consent

Exclusion Criteria:

* Minor patients
* Organ transplant
* Immunosuppressive drugs, other than corticosteroids
* Patients who decline participating to the assay
* Persons placed under legal protection, guardianship
* Pregnant woman
* Subject participating in another search including a exclusion period still in progress at pre-inclusion

Primary outcomes:
measure: Quantify in whole blood presence of PAMP during a septic shock,
timeFrame: Follow-up during 30 days
Secondary outcomes:
measure: Compare accuracy of Fc-MBL ELISA PAMP assay to CRP and PCT during septic shock.
timeFrame: Follow-up during 30 days
measure: Study PAMP's kinetic during septic shock from various origins
timeFrame: Follow-up during 30 days
measure: Identify patients who could beneficiate to a dialysis-like therapy
timeFrame: Follow-up during 30 days
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospital Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Eric Oswald, MD
role: PRINCIPAL_INVESTIGATOR
References: