Influence of Acute Respiratory Distress Syndrome (ARDS) and Severe Sepsis on sRAGE Levels in ICU Patients

Soluble Form of the Receptor for Advanced Glycation End Products (sRAGE) Levels in the Pulmonary Edema Fluid and Plasma From ICU Patients With ALI/ARDS and Severe Sepsis : an Observational Prospective Study.

sRAGE, the soluble form of the receptor for advanced glycation end products, is a novel marker of alveolar epithelial type I cell injury, but is also involved in acute systemic inflammation. The purpose of this observational prospective study is to determine whether sRAGE could be used in an ICU setting as a potential diagnostic and prognostic marker during ALI/ARDS, regardless of associated severe sepsis or septic shock.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Acute Respiratory Distress Syndrome; Acute Lung Injury; Severe Sepsis; Mechanical Ventilation
• Intervention / Treatment: Other: sRAGE

Detailed Description

BACKGROUND:

The receptor for advanced glycation end products (RAGE was recently identified as a promising new marker of alveolar type I cell injury. RAGE is a member of the immunoglobulin superfamily that acts as a multiligand receptor and is involved in propagating inflammatory responses. While the precise function of RAGE remains unclear, the elevated levels of RAGE, and its soluble isoform sRAGE, correlate with severity of ALI/ARDS in human and animal studies, and RAGE levels could reflect impaired alveolar fluid clearance. Thus, it is possible that elevated levels of RAGE in ALI/ARDS derive in part from RAGE's role in systemic inflammatory cascades rather than purely from its release from alveolar type I cells.

DESIGN NARRATIVE:

This observational prospective clinical study will describe and compare sRAGE levels in the alveolar edema fluid and in the plasma from ICU patients enrolled within the first 24 hours after onset of ALI/ARDS and/or severe sepsis/septic shock, and from patients under mechanical ventilation (control group). Edema fluid and plasma samples will be collected simultaneously on day 1, day 3, day 6, and day 28 (or at ICU discharge), in order to describe kinetics of evolution of sRAGE levels. Undiluted pulmonary edema fluid samples will be collected in intubated patients only, and blood samples will be gathered from an indwelling arterial catheter. The concentrations of sRAGE will be measured in duplicate by ELISA.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • CHU Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Definied population

Description

Inclusion Criteria:

• ICU patients under mechanical ventilation
• Patients within the first 24 hours after onset of ALI/ARDS according to the 1994 American-European Consensus Conference (AECC)
• Patients within the first 24 hours after onset of severe sepsis or septic shock according to the 1992 ACCP/SCCM Consensus Conference

Exclusion Criteria:

• Pregnancy
• Acute exacerbation of diabetes
• Dialysis for end-stage kidney disease
• Alzheimer's disease
• Amyloidosis
• Evolutive neoplastic lesion

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control group	Other: sRAGE; The purpose of this observational prospective study is to determine wether sRAGE could be used in an ICU setting as a potential diagnostic and prognostic marker during ALI/ARDS, regardless of associated severe sepsis or septic shock

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
sRAGE levels in the plasma from ICU patients within the first 24 hours after onset of ALI/ARDS or severe sepsis/septic shock	within the first 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
To describe kinetics of evolution of sRAGE levels in ICU patients with ALI/ARDS and severe sepsis/septic shock	in UCU patients

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Matthieu JABAUDON, MD, University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Jabaudon M, Blondonnet R, Roszyk L, Bouvier D, Audard J, Clairefond G, Fournier M, Marceau G, Dechelotte P, Pereira B, Sapin V, Constantin JM. Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2015 Jul 15;192(2):191-9. doi: 10.1164/rccm.201501-0020OC.
• Jabaudon M, Futier E, Roszyk L, Chalus E, Guerin R, Petit A, Mrozek S, Perbet S, Cayot-Constantin S, Chartier C, Sapin V, Bazin JE, Constantin JM. Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients. Crit Care Med. 2011 Mar;39(3):480-8. doi: 10.1097/CCM.0b013e318206b3ca.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (ESTIMATE): December 19, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): October 1, 2013
• Last Update Submitted That Met QC Criteria: September 30, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Septic shock; Mechanical ventilation; Severe sepsis; Acute respiratory distress syndrome (ARDS); Intensive Care Unit (ICU); Receptor for advanced glycation end products (RAGE); Soluble RAGE (sRAGE); Acute Lung Injury (ALI); Alveolar epithelium
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Wounds and Injuries; Disease; Infant, Newborn, Diseases; Shock; Infant, Premature, Diseases; Thoracic Injuries; Sepsis; Toxemia; Syndrome; Shock, Septic; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: CHU-0042