Use of Fc-MBL to Detect and Monitor the Presence of PAMPs During Septic Shock (Fc-MBL/PAMPs)

Use of Fc Mannose-Binding Lectin to Detect and Monitor the Presence of Pathogen-Associated Molecular Patterns During Septic Shock

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.

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Biological: Blood Test

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric Oswald, MD; Phone Number: 33 5 67 69 04 17; Email: oswald.e@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France, 31059
    • Recruiting
    • University Hospital Toulouse
    • Contact: Eric Oswald, MD; Phone Number: 33 5 67 69 04 17; Email: oswald.e@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Patient with Septic Shock; Patient Hospitalized in Intensive Care Unit for sepsis of any etiology. The number of follow-up visits will not be changed compared to usual patient follow-up hospitalized in the intensive care unit but there will be blood testing more frequently

Biological: Blood Test; Addition to the current care but during the normal follow-up visit : At the entrance to the service: search for bacterial 16S RNA in the blood; Additional blood tests (4) at T6-12-18 and 36h; At each visit: Sampling of an additional heparinized blood tube for the assay PAMPs.; 1 time per day: Assay of CRP and PCT from samples taken in common practice; J30: Assessment of the vital status of the patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify in whole blood presence of PAMP during a septic shock,	Quantify in whole blood presence of PAMP during a septic shock, using Fc-MBL ELISA :t o improve diagnostic by distinguishing a septic shock from another shock, and stating prognosis by studying PAMP kinetic under antibiotherapy.	Follow-up during 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare accuracy of Fc-MBL ELISA PAMP assay to CRP and PCT during septic shock.	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 and PCT. Its specificity will be evaluated by comparing its levels during septic and non-septic shocks.	Follow-up during 30 days
Study PAMP's kinetic during septic shock from various origins	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 and PCT. Its specificity will be evaluated by comparing its levels during septic and non-septic shocks.	Follow-up during 30 days
Identify patients who could beneficiate to a dialysis-like therapy	identifying patients with high levels of PAMPs for dialysis-like sepsis therapies	Follow-up during 30 days

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Harvard Medical School (HMS and HSDM)
• Investigators: Principal Investigator: Eric Oswald, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 18, 2018
• Primary Completion (ANTICIPATED): July 18, 2019
• Study Completion (ANTICIPATED): July 18, 2019

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: March 5, 2018
• First Posted (ACTUAL): March 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Mannose-Binding Lectin, PAMPs,
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: RC31/17/0157; 2017-A01686-47 (OTHER: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No