Friedemann J H Taut1, Gerd Rippin2, Peter Schenk3, George Findlay4, Wilhelm Wurst1, Dietrich Häfner1, James F Lewis5, Werner Seeger6, Andreas Günther6, Roger G Spragg7. 1. Department of Clinical Research, Nycomed, Konstanz, Germany. 2. Department of Biometrics, Omnicare Clinical Research, Cologne, Germany. 3. Department of Internal Medicine IV, General Hospital Vienna, Vienna, Austria. 4. Department of Intensive Care, University Hospital of Wales, Cardiff, UK. 5. St. Joseph's Health Center, University of Western Ontario, London, ON, Canada. 6. Department of Pulmonology, Justus-Liebig University, Giessen, Germany. 7. Division of Pulmonary and Critical Care Medicine, University of California San Diego and the San Diego VA Healthcare System, La Jolla, CA. Electronic address: rspragg@ucsd.edu.
Abstract
BACKGROUND: Studies to date have shown no survival benefit for the use of exogenous surfactant to treat patients with the ARDS. To identify specific patient subgroups for future study, we performed an exploratory post hoc analysis of clinical trials of recombinant surfactant protein-C (rSP-C) surfactant (Venticute; Nycomed GmbH; Konstanz, Germany). METHODS: We performed a pooled analysis of all five multicenter studies in which patients with ARDS due to various predisposing events were treated with rSP-C surfactant. Patients received either usual care (n = 266) or usual care plus up to four intratracheal doses (50 mg/kg) of rSP-C surfactant (n = 266). Factors influencing the study end points were analyzed using descriptive statistics, analysis of covariance, and logistic regression models. RESULTS: ARDS was most often associated with pneumonia or aspiration, sepsis, and trauma or surgery. For the overall patient population, treatment with rSP-C surfactant significantly improved oxygenation (p = 0.002) but had no effect on mortality (32.6%). Multivariate analysis showed age and acute physiology and chronic health evaluation (APACHE) II score to be the strongest predictors of mortality. In the subgroup of patients with severe ARDS due to pneumonia or aspiration, surfactant treatment was associated with markedly improved oxygenation (p = 0.0008) and improved survival (p = 0.018). CONCLUSIONS:rSP-C surfactant improved oxygenation in patients with ARDS irrespective of the predisposition. Post hoc evidence of reduced mortality associated with surfactant treatment was obtained in patients with severe respiratory insufficiency due to pneumonia or aspiration. Those patients are the focus of a current randomized, blinded, clinical trial with rSP-C surfactant.
RCT Entities:
BACKGROUND: Studies to date have shown no survival benefit for the use of exogenous surfactant to treat patients with the ARDS. To identify specific patient subgroups for future study, we performed an exploratory post hoc analysis of clinical trials of recombinant surfactant protein-C (rSP-C) surfactant (Venticute; Nycomed GmbH; Konstanz, Germany). METHODS: We performed a pooled analysis of all five multicenter studies in which patients with ARDS due to various predisposing events were treated with rSP-C surfactant. Patients received either usual care (n = 266) or usual care plus up to four intratracheal doses (50 mg/kg) of rSP-C surfactant (n = 266). Factors influencing the study end points were analyzed using descriptive statistics, analysis of covariance, and logistic regression models. RESULTS: ARDS was most often associated with pneumonia or aspiration, sepsis, and trauma or surgery. For the overall patient population, treatment with rSP-C surfactant significantly improved oxygenation (p = 0.002) but had no effect on mortality (32.6%). Multivariate analysis showed age and acute physiology and chronic health evaluation (APACHE) II score to be the strongest predictors of mortality. In the subgroup of patients with severe ARDS due to pneumonia or aspiration, surfactant treatment was associated with markedly improved oxygenation (p = 0.0008) and improved survival (p = 0.018). CONCLUSIONS:rSP-C surfactant improved oxygenation in patients with ARDS irrespective of the predisposition. Post hoc evidence of reduced mortality associated with surfactant treatment was obtained in patients with severe respiratory insufficiency due to pneumonia or aspiration. Those patients are the focus of a current randomized, blinded, clinical trial with rSP-C surfactant.
Authors: Hisatsugu Goto; Julie G Ledford; Sambuddho Mukherjee; Paul W Noble; Kristi L Williams; Jo Rae Wright Journal: Am J Respir Crit Care Med Date: 2010-02-18 Impact factor: 21.405
Authors: Marija Kojicic; Guangxi Li; Andrew C Hanson; Kun-Moo Lee; Lokendra Thakur; Jayanth Vedre; Adil Ahmed; Larry M Baddour; Jay H Ryu; Ognjen Gajic Journal: Crit Care Date: 2012-12-12 Impact factor: 9.097
Authors: M Isabel García-Laorden; Felipe Rodríguez de Castro; Jordi Solé-Violán; Olga Rajas; José Blanquer; Luis Borderías; Javier Aspa; M Luisa Briones; Pedro Saavedra; J Alberto Marcos-Ramos; Nereida González-Quevedo; Ithaisa Sologuren; Estefanía Herrera-Ramos; José M Ferrer; Jordi Rello; Carlos Rodríguez-Gallego Journal: Crit Care Date: 2011-02-10 Impact factor: 9.097