Context: Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS).

Objective: To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS.

Design, setting, and patients: The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia.

Interventions: Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation.

Main outcome measures: The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning.

Results: Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19).

Conclusion: Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia.

Trial registration: clinicaltrials.gov Identifier: NCT00159939.