A Search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: a pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute).
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.
Taut
Friedemann J H
FJH
Department of Clinical Research, Nycomed, Konstanz, Germany.
Rippin
Gerd
G
Department of Biometrics, Omnicare Clinical Research, Cologne, Germany.
Schenk
Peter
P
Department of Internal Medicine IV, General Hospital Vienna, Vienna, Austria.
Findlay
George
G
Department of Intensive Care, University Hospital of Wales, Cardiff, UK.
Wurst
Wilhelm
W
Department of Clinical Research, Nycomed, Konstanz, Germany.
Häfner
Dietrich
D
Department of Clinical Research, Nycomed, Konstanz, Germany.
Lewis
James F
JF
St. Joseph's Health Center, University of Western Ontario, London, ON, Canada.
Seeger
Werner
W
Department of Pulmonology, Justus-Liebig University, Giessen, Germany.
Günther
Andreas
A
Department of Pulmonology, Justus-Liebig University, Giessen, Germany.
Spragg
Roger G
RG
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.
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007322:Instillation, Drug; D008297:Male; D008875:Middle Aged; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D014132:Trachea; D016896:Treatment Outcome
D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C521929:Venticute