Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis-猫眼课题宝

DOI：

10.1136/gut.48.1.62

发表时间：

2001-01-01

期刊：

GUT

影响因子：

24.5

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Johnson, CD;Kingsnorth, AN;Curtis, LD

背景-血小板活化因子（PAF）被认为可以增强急性胰腺炎全身炎症反应综合征（SIRS）的关键介质的活性，导致多器官功能障碍综合征。我们测试的假设，一个有效的PAF拮抗剂，lexipafant，可以抑制全身炎症反应综合征和减少器官衰竭在重症急性pancreat. Methods，我们进行了一项随机，双盲，安慰剂对照，多中心试验lexipafant（100毫克/24小时静脉注射7天内开始的症状发作72小时），涉及290例患者的APACHE II评分>6。功效计算假设并发症将从40%减少到24%。研究的次要终点包括器官衰竭的严重程度、炎症反应的标志物和死亡率。研究结果-总体而言，安慰剂组80/138（58%）患者和来昔帕芬组85/148（57%）患者出现一个或多个器官衰竭。44%的患者在进入研究时发生器官衰竭，这一意外发现使主要假设无效;只有39例（14%）发生了新的器官衰竭。仅在第3天，来昔帕芬组的器官衰竭评分降低：中位变化为-1（范围为-4至+8），而安慰剂组为0（-4至+10）（p=0.04）。来昔帕芬组中全身性脓毒症影响的患者较少（13/138 v4/148; p=0.023）。安慰剂组41/138例（30%）患者和来昔帕芬组30/148例（20%; p=0.065）患者发生局部并发症;分别有19例（14%）和8例（5%）患者出现假性囊肿（p=0.025）。急性胰腺炎引起的死亡没有显著差异。白细胞介素8（中性粒细胞活化的标志物）和E-选择素（内皮损伤的标志物）在来昔帕芬组下降更快（均为p

Background-Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis.Methods-We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate.Findings-Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p

Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis

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