RANDOMIZED, DOUBLE-BLIND PHASE-II TRIAL OF LEXIPAFANT, A PLATELET-ACTIVATING-FACTOR ANTAGONIST, IN HUMAN ACUTE-PANCREATITIS

The aims of the study were to determine whether the platelet-activatin g factor antagonist Lexipafant could alter the clinical course and sup press the inflammatory response of human acute pancreatitis. In a doub le-blind, placebo-controlled study 83 patients were randomized to rece ive Lexipafant 60 mg intravenously for 3 days, or placebo. Clinical pr ogression was assessed by daily Acute Physiology And Chronic Health Ev aluation (APACHE) II score and organ failure score (OFS). The magnitud e of the inflammatory response on days 1-5 was assessed by serial meas urement of interleukin (IL) 8, IL-6, E-selectin, polymorphonuclear ela stase-alpha(1)-antitrypsin (PMNE-alpha(1)-AT), and C-reactive protein (CRP). At entry, patients receiving Lexipafant (n=42) or placebo (n=41 ) were matched for age and sex, aetiology, APACHE II score and OFS. Th e disease was classified as severe in 29 patients (APACHE II score eig ht or more). There was a significant reduction in the incidence of org an failure (P = 0.041) and in total OFS (P = 0.048) at the end of medi cation (72 h). During this time seven of 12 patients with severe acute pancreatitis who had Lexipafant recovered from an organ failure; only two of 11. with severe acute pancreatitis who had placebo recovered f rom an organ failure and two others developed new organ failure. Lexip afant treatment significantly reduced serum IL-8 (P=0.038), and IL-6 d eclined on day 1. Plasma PMNE-alpha(1)-AT complexes peaked on day 1; t he gradual fall to baseline over 5 days observed in controls did not o ccur in patients given Lexipafant. No effect was observed on serum CRP . This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis.