1Division of Pulmonary and Critical Care Medicine, University of California San Diego and San Diego Veterans Affairs Healthcare System, San Diego, California;2Nycomed GmbH, Konstanz, Germany;3St Joseph's Health Center, University of Western Ontario, London, Ontario, Canada;4Department of Internal Medicine IV, General Hospital Vienna, Vienna, Austria;5Department of Pulmonary and Critical Care, Justus-Liebig-University, Giessen, Germany;6Intermountain Medical Center and the University of Utah, Salt Lake City, Utah;7Eastern Idaho Medical Center, Idaho Falls, Idaho; and8General Hospital of Athens, Athens, Greece
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Rationale:Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality.Objectives:Determine the clinical benefit of administering an rSP-C-based synthetic surfactant to patients with severe direct lung injury due to pneumonia or aspiration.Methods:A prospective randomized blinded study was performed at 161 centers in 22 countries. Patients were randomly allocated to receive usual care plus up to eight doses of rSP-C surfactant administered over 96 hours (n = 419) or only usual care (n = 424).Measurements and Main Results:Mortality to 28 days after treatment, the requirement for mechanical ventilation, and the number of nonpulmonary organ failure-free days were not different between study groups. In contrast to prior studies, there was no improvement in oxygenation in patients receiving surfactant compared with the usual care group. Investigation of the possible reasons underlying the lack of efficacy suggested a partial inactivation of rSP-C surfactant caused by a step of the resuspension process that was introduced with this study.Conclusions:In this study, rSP-C-based surfactant was of no clinical benefit to patients with severe direct lung injury. The unexpected lack of improvement in oxygenation, coupled with the results ofin vitrotests, suggest that the administered suspension may have had insufficient surface activity to achieve clinical benefit.Clinical trial registered with www.clinicaltrials.gov (NCT00074906).