Lexipafant and Acute Pancreatitis: A Critical Appraisal of the Clinical Trials Fikri M. Abu-Zidan and John A. Windsor* From the Department of Surgery, Faculty of Medicine and Health Sciences, United Arab Emirates University, UAE and the Pancreatitis Research Group*, Department of Surgery, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand Eur J Surg 2002; 168: 215–219 ABSTRACT The recent clinical trials of lexipafant in the treatment of acute pancreatitis were undertaken with considerable optimism. It was expected that this single agent anticytokine would reduce the morbidity and mortality of this disease. Published clinical trials of lexipafant (BB-882) in acute pancreatitis were retrieved by MEDLINE, EM Base, and Science Citation Index. The critical appraisal included the question asked, design of the study, group and selection of patients, results, and statistical analysis. The historical sequence of the trials and the impact of commerce on their performance were highlighted. Lexipafant did not reduce mortality in severe acute pancreatitis. Comparison between the trials is difcult because of changes in study groups and dose. The clinical trials were designed without the benet of open discussion of the preliminary pharmacological studies. The results of the trials have not been communicated in an open, timely, and systematic manner, probably because of commercial constraints. Key words: acute pancreatitis, lexipafant, BB-882, platelet-activating factor antagonist. INTRODUCTION Lexipafant (BB-882), which was developed by British Biotechnology (Oxford, UK), is one of the most potent platelet-activating factor (PAF) receptor antagonists (4). PAF is an important proximal proinammatory mediator which acts through specic receptors and its concentration is raised in a number of diseases (25). The ubiquity of its receptors on the surface of and within normal cells reects its physiological impor- tance. PAF is involved in the regulation of different physiological functions including maintenance of normal blood pressure and induction of labour (20, 25). Acute pancreatitis is a classic inammatory disease. Although there have been several advances in its metabolic management, it is still a disease that has no specic treatment and is responsible for appreciable mortality and economic burden (28). The decision to subject lexipafant to clinical trials in the treatment of acute pancreatitis was ambitious because there has seldom been a disease for which there have been so many failed treatments and attempts to identify reliable early prognostic markers (27). This reects our relatively poor understanding of the fundamental pathophysiolog y of acute pancreatitis. The intention of this paper is to provide an independent critique of the conduct, communication, and commerce of the important clinical trials of lexipafant in acute pancreatitis. The efforts made in conducting these trials were immense and are acknowl- edged. We also acknowledge that it is easy to criticise with the wisdom of hindsight. Nevertheless, we think that the trials warrant dispassionate discussion so that we can learn from them. This is important for those who seek to improve outcome for patients through the conduct of clinical trials and for those who seek prot from the introduction of new treatments. METHODS Published clinical trials of lexipafant (BB-882) in acute pancreatitis or sepsis were retrieved by searching MEDLINE, EMBase and Science Citation Index. The critical appraisal included the question asked, design of the study, group of patients and their selection, and statistical analysis. The results of the pancreatitis trials were combined. Data for mortality were analysed using Fisher’s exact test or the chi square test, as appropriate. RESULTS AND DISCUSSION The clinical trials The rst published clinical trial of lexipafant in acute pancreatitis was from 5 centres in the United Kingdom and included patients with both mild and severe disease (14) (Table I). Lexipafant signicantly reduced the Ó 2002 Taylor & Francis. ISSN 1102–4151 Eur J Surg 168 REVIEW ARTICLE