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

NCT ID: NCT01600651

Last Updated: 2013-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2013-10-31

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 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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

Receptor for advanced glycation end products (RAGE); Soluble RAGE (sRAGE); Recruitment Maneuver; Acute respiratory distress syndrome (ARDS); Alveolar epithelium; Electrical Impedance Tomography; Mechanical ventilation; Intensive Care Unit (ICU)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Recruitment maneuver (RM) sham group

when recruitment maneuver sequence precedes a sham evaluation period

Group Type: SHAM_COMPARATOR

Recruitment Maneuver (RM) sham group

Intervention Type: OTHER

It 's when RM sequence precedes a shame evaluation period

Sham Recruitment (RM) maneuver group

a group in which patients receive a sham sequence before the RM sequence

Group Type: SHAM_COMPARATOR

Sham recruitment maneuver (RM) group

Intervention Type: OTHER

Group in which patients receive a sham sequence before the RM sequence

Interventions

Recruitment Maneuver (RM) sham group

It 's when RM sequence precedes a shame evaluation period

Intervention Type: OTHER

Sham recruitment maneuver (RM) group

Group in which patients receive a sham sequence before the RM sequence

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 25792206 (View on PubMed)

Other Identifiers

CHU-0119

Identifier Type: -

Identifier Source: org_study_id