An. Kingsnorth et al., RANDOMIZED, DOUBLE-BLIND PHASE-II TRIAL OF LEXIPAFANT, A PLATELET-ACTIVATING-FACTOR ANTAGONIST, IN HUMAN ACUTE-PANCREATITIS, British Journal of Surgery, 82(10), 1995, pp. 1414-1420
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.