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Antimicrobial Agents and Chemotherapy, March 2000, p. 693-696, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Double-Blind Placebo-Controlled Study of an Infusion of Lexipafant (Platelet-Activating Factor Receptor Antagonist) in Patients with Severe Sepsis

Yupin Suputtamongkol,1,* Sunanta Intaranongpai,1,dagger Michael D. Smith,2,3,Dagger Brian Angus,2,3 Wipada Chaowagul,4 Chairat Permpikul,1 Julie A. Simpson,2,3 Amorn Leelarasamee,1 Lloyd Curtis,5 and Nicholas J. White2,3

Department of Medicine, Faculty of Medicine Siriraj Hospital,1 and Faculty of Tropical Medicine,2 Mahidol University, Bangkok, and Department of Medicine, Sappasitprasong Hospital, Ubon Ratchatani,4 Thailand, and Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University,3 and British Bio-technology Limited,5 Oxford, United Kingdom

Received 27 October 1998/Returned for modification 15 August 1999/Accepted 1 December 1999

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.

* Corresponding author. Mailing address: Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Phone: 66 2 419 7301. Fax: 66 2 412 5994. E-mail: siysp{at}mahidol.ac.th.

dagger Present address: Department of Medicine, Surin Hospital, Surin, Thailand.

Dagger Present address: Taunton Hospital, Musgrave Park, Taunton, United Kingdom.

Antimicrobial Agents and Chemotherapy, March 2000, p. 693-696, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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