Clinical Trial: Diffuse Acute Respiratory Distress Syndrome (ARDS), Recruitment Maneuver, and sRAGE (DAMAGE Study)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effects Of A Recruitment Maneuver On Plasma Levels of sRAGE, The Soluble Form of The Receptor For Advanced Glycation End Products, In Patients With Diffuse Acute Respiratory Dist

Brief Summary: RAGE, the receptor for advanced glycation end products, is a novel marker of alveolar epithelial type I cell injury, and soluble RAGE (sRAGE) is elevated in the plasma and in the pulmonary edema fluid from patients with ALI/ARDS. Few data are available about the influence of ventilatory interventions on levels of sRAGE in the setting of ALI/ARDS. The purpose of this prospective monocentric randomized controlled cross-over study is to describe the effects of a recruitment maneuver (RM) on plasma sRAGE levels during diffuse ARDS.

Detailed Summary:

BACKGROUND:

The receptor for advanced glycation end products (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 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 higher sRAGE levels could reflect impaired alveolar fluid clearance. Lung morphology, as assessed by loss of aeration distribution patterns on computed tomography (CT) scan, predicts the response to recruitment maneuvers in patients with ARDS: patients presenting with nonfocal (diffuse) lung morphology are more likely to respond to a RM, resulting in an increase in arterial oxygenation, net alveolar fluid clearance, and significant alveolar recruitment as revealed by pressure-volume curve analysis.

DESIGN NARRATIVE:

The purpose of this prospective, randomized and controlled, cross-over study is to compare the effects of a RM on plasma sRAGE levels (measured 5 minutes before, 5 minutes, 30 minutes, 1 hour, 4 hours and 6 hours after the RM) and plasma sRAGE levels measured during a "sham" or "control" sequence, in patients with diffuse ARDS.

Mechanically ventilated ICU patients with ARDS criteria (based on the 1994 American-European Consensus Conference definition for ARDS) and nonfocal CT scan lung morphology will be included within 24 hours of disease onset. Then, patients will be randomized into 2 groups: a "RM-SHAM" group when RM sequence precedes a sham evaluation period, and a "SHAM-RM" group, in which patients receive a sham sequence be
Sponsor: University Hospital, Clermont-Ferrand

Current Primary Outcome: Plasma sRAGE [ Time Frame: 1 hour after the RM ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Plasma sRAGE in responders and non-responders to RM [ Time Frame: 5 minutes before, then 5 minutes, 30 minutes, 4 hours and 6 hours after RM ]
  • Kinetics of sRAGE after RM [ Time Frame: 5 minutes before, and 5 minutes, 30 minutes, 1 hour, 4 hours and 6 hours after RM and after a sham period ]
  • Predictive value of baseline sRAGE on the response to RM [ Time Frame: 5 minutes before, and 5 minutes, 30 minutes, 1 hour, 4 hours and 6 hours after RM ]
  • Correlation of plasma sRAGE and response to RM with lung aeration [ Time Frame: 5 minutes before, and 5 minutes, 30 minutes, 1 hour, 4 hours and 6 hours after RM or sham period ]
  • Risk of RM-related pulmonary bacterial translocation [ Time Frame: 5 minutes before and 30 minutes after RM ]


Original Secondary Outcome: Same as current

Information By: University Hospital, Clermont-Ferrand

Dates:
Date Received: April 24, 2012
Date Started: April 2012
Date Completion:
Last Updated: October 1, 2013
Last Verified: October 2013