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Acute pancreatitis
Published in David Westaby, Martin Lombard, Therapeutic Gastrointestinal Endoscopy A problem-oriented approach, 2019
Studies have demonstrated that administration of systemic antibiotics early in the course of an attack may reduce the incidence of septic complications, particularly infection involving areas of pancreatic necrosis [25,26]. Thus a patient with severe acute pancreatitis should be started on an intravenous broad-spectrum antibiotic at the time of diagnosis, probably either imipenem or cefuroxime. A recent placebo-controlled, randomized, multicentre study has shown that lexipafant – a potent antagonist of platelet activating factor (PAF) which is a mediator of SIRS – significantly reduces organ failure scores and mortality in severe acute pancreatitis, but only if administered within the first 48 h of the onset of symptoms [27].
Pancreatitis and pancreatic insufficiency
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Stefan Kahl, Peter Malfertheiner
Lexipafant, a potent antagonist of platelet activating factor (PAF), was also a new promising candidate. It was probably effective in experimentally-induced pancreatitis in rats, and an initial pilot study in humans showed reduced pancreatic and extrapancreatic inflammation, as well as a reduction in organ complications.20 However, in a recent large multicentre study, a beneficial effect was not confirmed.21
The effect of thymosin α1 for prevention of infection in patients with severe acute pancreatitis
Published in Expert Opinion on Biological Therapy, 2018
Na Yang, Lu Ke, Zhihui Tong, Weiqin Li
To date, available immunomodulatory therapies, such as IL-10 and infliximab (monoclonal TNF α antibody) have all been found to be beneficial in experimental pancreatitis models. In contrast to experimental findings, few of these were successfully confirmed in clinical studies (Table 1) [56–73]. Besides thymosin α1, there were two immunomodulatory agents (lexipafant and octreotide) being applied in clinical trials. As a profound platelet-activating factor antagonist, lexipafant was thought to be able to modulate the cytokine response of AP. However, the results of clinical trials of lexipafant in AP have changed with the variation in dose and study design (Table 1) [59–61]. Octreotide, an analog of somatostatin, can significantly inhibit exocrine pancreatic secretion. The current pharmacology tended to consider octreotide as a vital inhibitors of inflammatory injury in the treatment of AP. Similar to the clinical results of lexipafant, present evidences did not support the benefit of octreotide in the major outcomes (Table 1) [62–72].
Trends and recent developments in pharmacotherapy of acute pancreatitis
Published in Postgraduate Medicine, 2023
Juliana Hey-Hadavi, Prasad Velisetty, Swapnali Mhatre
Lexipafant is a PAF receptor antagonist introduced for the treatment of AP. The efficacy of lexipafant was rigorously tested in a double-blind, placebo-controlled, multicenter, Phase 3 study. There was a high frequency of organ failure within 72 hours of the onset of symptoms and consequently, the study could not achieve its primary endpoint i.e. reduction in the frequency of organ failure. Thus, lexipafant treatment failed to reduce new organ failure [82].