Clinical trial NCT00811629: Influence of Acute Respiratory Distress Syndrome (ARDS) and Severe Sepsis on sRAGE Levels in ICU Patients
Official title: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lung Injury
Acute Respiratory Distress Syndrome
Severe Sepsis
Septic Shock
Mechanical Ventilation
Keywords: Receptor for advanced glycation end products (RAGE)
Soluble RAGE (sRAGE)
Acute Lung Injury (ALI)
Acute respiratory distress syndrome (ARDS)
Severe sepsis
Septic shock
Alveolar epithelium
Mechanical ventilation
Intensive Care Unit (ICU)
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2008-12-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Definied population

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: sRAGE levels in the plasma from ICU patients within the first 24 hours after onset of ALI/ARDS or severe sepsis/septic shock
timeFrame: within the first 24 hours
Secondary outcomes:
measure: To describe kinetics of evolution of sRAGE levels in ICU patients with ALI/ARDS and severe sepsis/septic shock
timeFrame: in UCU patients
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Matthieu JABAUDON, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.