1Department of Intensive Care Medicine, University Medical Center Utrecht, the Netherlands;2Department of Adult Critical Care, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom;3Department of Medicine, Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, Canada;4Department of Critical Care Medicine, University Hospital of Wales, Cardiff, United Kingdom;5Multidisciplinary Intensive Care Unit, La Pitié-Salpêtrière Hospital, UPMC University, Paris 06, France;6Service Ranimation, Centre Hospitalier, Bourg En Bresse, France;7Department of Anesthesiology, Intensive Care & Pain Management, St. Antonius Hospital, Nieuwegein, The Netherlands;8LEO Pharma A/S, Ballerup, Denmark; and9Department of Anesthesia and Intensive Care Medicine, Charite, Humboldt-University, Berlin, Germany
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Rationale:Compositional changes in surfactant and/or decreased surfactant content of the lungs are common features in patients with acute respiratory failure. Instillation of exogenous surfactant into the lungs of neonates with respiratory distress syndrome or pediatric patients with acute respiratory distress syndrome (ARDS) has resulted in improved survival.Objectives:We conducted this trial to determine whether the instillation of exogenous surfactant would improve the Day 28 outcome of adult patients with acute lung injury (ALI) or ARDS.Methods:A total of 418 patients with ALI and ARDS were included in an international, multicenter, stratified, randomized, controlled, open, parallel-group study. We randomly assigned 418 patients to receive usual care either with or without instillation of exogenous natural porcine surfactant HL 10 as large boluses.Measurements and Main Results:The primary endpoint was death rate before or on Day 28. Secondary endpoints were adverse event and death rate on day 180. The 28-day death rate in the usual care group was 24.5% compared with 28.8% in the HL 10 group. The estimated odds ratio for death at Day 28 in the usual care group versus the HL 10 group was 0.75 (95% CI, 0.48–1.18; P = 0.22). The most common adverse events related to HL 10 administration were temporary hypoxemia defined as oxygen saturation less than 88% (51.9% in HL 10 group vs. 25.2% in usual care) and hypotension defined as mean arterial blood pressure less than 60 mm Hg (34.1% in HL 10 group vs. 17.1% in usual care).Conclusions:In this study, instillation of a large bolus of exogenous natural porcine surfactant HL 10 into patients with acute lung injury and ARDS did not improve outcome and showed a trend toward increased mortality and adverse effects.Clinical trial registered with www.clinicaltrials.gov (NCT 00742482).