Recombinant platelet-activating factor acetylhydrolase to prevent XXXX and mortality in severe @entity295 : Phase IIb, multicenter, randomized, placebo-controlled, clinical trial.

@entity1 @entity295 @entity649 @entity6511 @entity1729 @entity204
OBJECTIVE: Platelet-activating factor (PAF) is a potent proinflammatory mediator implicated in the pathogenesis of both severe @entity295 and @entity649 . One of the regulatory pathways for PAF involves degradation to the inactive metabolite lyso-PAF by the enzyme @entity6511 ( @entity6511 ). Because reduced concentrations of the natural form of @entity6511 have been reported in septic @entity1 , the present study was conducted to determine whether treatment with recombinant @entity1 @entity6511 (rPAF-AH, Pafase) was safe when administered after the onset of severe @entity295 and whether it decreases the prevalence of @entity649 and 28-day all-cause mortality. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Thirty-three medical and surgical intensive care units located in the United States. @entity1 : A total of 127 @entity1 with severe @entity295 , but without established @entity649 , were enrolled in the study. Randomization occurred within 12 hrs of the onset of severe @entity295 . @entity1 then received 1.0 mg/kg rPAF-AH (n = 45), 5.0 mg/kg rPAF-AH (n = 39), or placebo (n = 43) administered intravenously, once daily, for five consecutive days. MEASUREMENTS AND MAIN RESULTS: Demographic and baseline clinical characteristics of the three treatment groups were similar, except for a significantly higher prevalence of @entity1729 as the cause of severe @entity295 in @entity1 treated with 1.0 mg/kg rPAF-AH. There were no treatment-related @entity204 , and the overall prevalence of adverse events was similar among rPAF-AH-treated and placebo-treated @entity1 . There were no significant differences in the prevalence of @entity649 among the three treatment groups. However, 28-day all-cause mortality was 21% in the 1.0 mg/kg rPAF-AH group, 28% in the 5.0 mg/kg rPAF-AH group, and 44% in the placebo group (overall chi-square p =.07; 1.0 mg/kg rPAF-AH vs. placebo, p =.03). A trend toward reduced multiple organ dysfunction also was observed in the 1.0 mg/kg rPAF-AH group compared with the placebo group (p =.11). CONCLUSION: The results from this study indicate that rPAF-AH was well tolerated and should be pursued as a potential new treatment to decrease mortality in @entity1 with severe @entity295 .
