Clinical Trial: Effect of Prone Positioning on Mortality in Patients With Severe and Persistent Acute Respiratory Distress Syndrome

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

Official Title: Effect of Prone Positioning on Mortality in Patients With Severe and Persistent Acute Respiratory Distress Syndrome

Brief Summary: We project to test the effect of prone position on mortality in severe ARDS patients (PaO2/FiO2<150 with FiO2 > or = 0.6 and positive end-expiratory pressure > or = 5 cmH2O). Ventilator will be set in accordance with current standards aiming at protecting the lungs from VALI. Patients will be randomized into two arms: prone group in which proning will be realized for at least 16 hours a day and supine group in which patients will stay in a semi-recumbent position. Primary end-point is 28-day mortality of all causes. Secondary end-points are 90-day mortality of all causes and incidence of ventilator-acquired pneumonia. Study sample was calculated to detect ability of proning to reduce mortality from 60 to 45% percent, at one-tailed alpha error of 5% and power of 90% and 230 patients are needed in each arm.

Detailed Summary: The acute respiratory distress syndrome (ARDS) is an acute respiratory failure characterized by bilateral pulmonary infiltrates on frontal chest radiography, arterial oxygen tension (Pao2) to fraction of inspired oxygen (FiO2) ratio of 200 or less, and absence of evidence for left atrial hypertension. In-hospital mortality remains high: from 40 to 60%. Typical pathological findings include disruption of the alveolar epithelium, diffuse alveolar damage, hyaline membranes and pulmonary inflammation. Gas exchange is severely altered making of invasive mechanical ventilation required in most of the cases. Mechanical ventilation should be judiciously set in order to protect the lung from ventilator- associated lung injury (VALI). VALI is commonly seen as the expression of two main alveolar strains. The well documented one to date is over distension of alveoli when high tidal volumes are used. A North-American randomized controlled trial (RCT) has demonstrated that using low tidal volumes (6 ml per kilo of predicted weight) results in a 22% decrease in mortality when compared with high tidal volumes (12 ml per kilo of predicted weight). As suggested by an ancillary study of this trial, a reduced pulmonary inflammation is one of the contributing factors of this result. Therefore, minimizing VALI is a primary therapeutic goal. Low lung volume VALI is the second potential mechanism, though less well documented. It is expected to result from repetitive collapse and reopening of terminal respiratory units. Experimental data suggest that proning can reduce VALI by homogenizing lung strains. In ARDS patients, proning is mainly used due to its ability to improve gas exchange in 60 to 70% of patients. Nonetheless, 3 RCTs failed to demonstrate a significant effect on mortality of proning in three clinical situations: 1: acute lung injury, 2: hypoxemic acute respiratory failure, 3: ARDS. Post hoc analysis of one of them has suggested an effect of proning on mortality for the most hy
Sponsor: Hospices Civils de Lyon

Current Primary Outcome: 28-day mortality from all causes [ Time Frame: 28 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome: 90-day mortality from all causes and incidence of ventilator-acquired pneumonia (VAP). [ Time Frame: 90 days ]

Original Secondary Outcome: Same as current

Information By: Hospices Civils de Lyon

Dates:
Date Received: September 10, 2007
Date Started: January 2008
Date Completion:
Last Updated: May 6, 2015
Last Verified: November 2011