A double-blind placebo-controlled study of an infusion of lexipafant (Platelet-activating factor receptor antagonist) in patients with severe sepsis.
Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom had positive blood cultures). Detailed serial clinical, biochemical, and cytokine measurements were performed. Lexipafant treatment was well tolerated. The 28-day mortality in the lexipafant group (61.4%) was similar to that in the placebo group (62.6%). There was also no evidence that lexipafant affected clinical or biochemical measures of disease severity or the profile of sequentially measured plasma cytokine levels. PAF may not have an important role in the pathogenesis of severe sepsis.
Suputtamongkol
Y
Y
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Intaranongpai
S
S
Smith
M D
MD
Angus
B
B
Chaowagul
W
W
Permpikul
C
C
Simpson
J A
JA
Leelarasamee
A
A
Curtis
L
L
White
N J
NJ
D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007773:Lactates / Q000097:blood; D007930:Leucine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality
D016207:Cytokines; D007093:Imidazoles; D007773:Lactates; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D007930:Leucine; C103289:lexipafant