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

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 Distress Syndrome (ARDS)

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.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Recruitment Maneuver (RM) sham group; Other: Sham recruitment maneuver (RM) group

Detailed Description

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 before the RM sequence. Patients will receive protective ventilation, as recommended, before, during and after evaluation periods. RM consists of the application of 40 cmH20 airway pressure for 40 seconds.

Blood will be sampled from an indwelling arterial catheter, in order to analyze arterial blood gases and sRAGE levels, 5 minutes before the RM (or a 40 second-long sham period), 5 minutes, 30 minutes, 1 hour, 4 hours and 6 hours after the RM (or a 40 second-long sham period). Electric impedance tomography will be evaluated 5 minutes before and 1 hour after the RM.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Chu Clermont-Ferrand

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:

• ICU patients under mechanical ventilation
• Patients within the first 24 hours after onset of ARDS according to the 1994 American-European Consensus Conference (AECC)
• PaO2/FiO2 ratio < 200 with external PEEP >5 cmH2O
• "Nonfocal" loss of aeration based on CT scan lung morphology analysis, as defined by the "CT scan ARDS study group" criteria

Exclusion Criteria:

• Pregnancy
• Acute exacerbation of diabetes
• Dialysis for end-stage kidney disease
• Alzheimer's disease
• Amyloidosis
• Evolutive neoplastic lesion
• Known or suspected history of allergy to cisatracurium
• Chronic respiratory disease requiring long term oxygen therapy or long term ventilation
• Confirmed or suspected elevated intracranial pressure
• Confirmed or suspected bronchopleural fistula, pneumothorax
• Persistent hemodynamic instability despite appropriate resuscitation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Recruitment maneuver (RM) sham group; when recruitment maneuver sequence precedes a sham evaluation period	Other: Recruitment Maneuver (RM) sham group; It 's when RM sequence precedes a shame evaluation period
Sham Comparator: Sham Recruitment (RM) maneuver group; a group in which patients receive a sham sequence before the RM sequence	Other: Sham recruitment maneuver (RM) group; Group in which patients receive a sham sequence before the RM sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma sRAGE	1 hour after the RM

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma sRAGE in responders and non-responders to RM	5 minutes before, then 5 minutes, 30 minutes, 4 hours and 6 hours after RM
Kinetics of sRAGE after RM	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	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	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	5 minutes before and 30 minutes after RM

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Jabaudon M, Hamroun N, Roszyk L, Guerin R, Bazin JE, Sapin V, Pereira B, Constantin JM. Effects of a recruitment maneuver on plasma levels of soluble RAGE in patients with diffuse acute respiratory distress syndrome: a prospective randomized crossover study. Intensive Care Med. 2015 May;41(5):846-55. doi: 10.1007/s00134-015-3726-0. Epub 2015 Mar 20.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: April 24, 2012
• First Submitted That Met QC Criteria: May 15, 2012
• First Posted (Estimate): May 17, 2012

Study Record Updates

• Last Update Posted (Estimate): October 7, 2013
• Last Update Submitted That Met QC Criteria: October 1, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Mechanical ventilation; Electrical Impedance Tomography; Acute respiratory distress syndrome (ARDS); Intensive Care Unit (ICU); Receptor for advanced glycation end products (RAGE); Soluble RAGE (sRAGE); Alveolar epithelium; Recruitment Maneuver
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CHU-0119