Predictive Values of Plasma Soluble RAGE Levels and RAGE Polymorphisms for the Onset of Acute Respiratory Distress Syndrome in Critically Ill Patients

Study Overview
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Brief Summary
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Current clinical prediction scores for acute respiratory distress syndrome (ARDS) have limited positive predictive value. No studies have evaluated predictive kinetics of plasma biomarkers and receptor for advanced glycation end products (RAGE) polymorphisms in a broad population of critically ill patients or as an adjunct to clinical prediction scores. The main objective of the investigators study is to evaluate the predictive values of plasma soluble RAGE levels for the onset of ARDS in a high risk population of patients admitted to the intensive care unit (ICU). One of the investigators goals is to improve early identification of patients at risk for ARDS in order to better implement preventive stategies prior to ARDS development. The primary outcome is the occurrence of ARDS during the first week after admission to the ICU.

Detailed Description
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BACKGROUND : ARDS is a major cause of morbidity and mortality in critically ill patients. Only few pharmacological treatments are available, with limited evidence of efficacy. The development of efficient preventive stategies is limited by the investigators inability to predict which patients are likely to develop ARDS. The Lung Injury predicition Score (LIPS) has been developed to identify patients at high risk for ARDS, but its predictive value remains limited. The receptor for advanced glycation end product (RAGE) is now identified as a marker of alveolar type I cell injury. RAGE is a member of the immunoglobulin superfamily that acts as a multiligand receptor which is involved in propagating inflammatory responses. Plasma levels of sRAGE are correlated with clinical and radiologic severity in ARDS patients. The investigators main objective is to assess the predictive values of plasma sRAGE and esRAGE levels, as well as their evolution over the first 24 hours after admission, for the onset of ARDS in high risk patients. The secondary objectives are to : to evaluate the predictive value of RAGE polymorphisms (_429 T/C, _374 T/A, 2184 A/G, Gly82Ser) for the onset of ARDS to evaluate the predictive value of maximal plasma levels of RAGE soluble forms for the onset of ARDS to test the relationship between RAGE polymorphisms and plasma sRAGE and esRAGE levels to test whether serial sRAGE measurements would improve the discrimination of the LIP Score or not to evaluate the prognostic value of plasma levels of RAGE soluble forms for : duration of mechanical ventilation, length of stay in the ICU and 30-day mortality. DESIGN NARRATIVE : The purpose of this prospective observational study is to test the values of RAGE polymorphism and soluble forms plasma levels for ARDS prediction in high risk ICU patients

Official Title
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Predictive Values of Plasma Soluble RAGE Levels and RAGE Polymorphisms for the Onset of Acute Respiratory Distress Syndrome in Critically Ill Patients

Conditions
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Intensive Care Unit, Population at High Risk for ARDS Development

Intervention / Treatment
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* Other: sRAGE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the ICU Patients presenting with risk factors for ARDS : high risk surgery, sepsis, shock, panceatitis, pneumonia, aspiration, drowning, massive transfusion, pulmonary contusion, serious burn, severe trauma. Informed consent Exclusion Criteria: Pregnancy Age < 18 years Criteria for ARDS at admission to the ICU Expected survival under 48 hours

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ARDS (Acute Respiratory Distress Syndrome)<br> | Other: sRAGE<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| development of ARDS | The development of ARDS, based on Berlin definition criteria, during the first week after admission to the ICU | during the first week after admission to the ICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma sRAGE and esRAGE levels |  | at ICU admission (Day 0) | 
| Plasma sRAGE and esRAGE levels |  | (Day 1) | 
| Evolution of plasma sRAGE levels |  | between day 0 and day 1 | 
| Maximal plasma levels of sRAGE and esRAGE |  | during the first 24 hours after ICU admission | 
| Development of ARDS |  | during at day 14 and day 30 after ICU admission | 
| Total duration of mechanical ventilation |  | at day 1 | 
| Length of stay in ICU |  | at day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soluble RAGE (sRAGE), Acute Respiratory Distress Syndrome (ARDS), Receptor for advanced glycation end products (RAGE), Gene polymorphisms, Biomarker