Efficacy of Linaclotide for Patients With Chronic Constipation
Efficacy of Linaclotide for Patients With Chronic Constipation
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DOI：
10.1053/j.gastro.2009.12.050
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发表时间：
2010-03-01
期刊：
影响因子：
29.4
通讯作者：
Johnston, Jeffrey M.
中科院分区：
文献类型：
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作者：
Lembo, Anthony J.;Kurtz, Caroline B.;Johnston, Jeffrey M.
背景与目的：利那洛肽是一种鸟苷酸环化酶- c受体的低吸收肽激动剂，在动物模型中刺激肠液分泌和转运，减轻疼痛。我们评估了一系列利那洛肽剂量对慢性便秘患者的安全性和有效性。方法：我们对310例慢性便秘患者进行了一项多中心、双盲、安慰剂对照、平行组研究。患者被随机分为75、150、300或600 μ g口服利那洛肽或安慰剂组，每天1次，持续4周。症状评估包括自发排便（SBMs）、完全排便、大便一致性、紧张、腹部不适和腹胀。评估便秘的严重程度、便秘的充分缓解、便秘的全面缓解、治疗满意度、生活质量、不良事件、临床实验室数据和心电图结果。结果：与安慰剂相比，所有剂量的利那洛肽均改善了每周SBM率（主要终点）；利那洛肽剂量为75、150、300和600 μ g时，总体每周SBMs数较基线分别增加2.6、3.3、3.6和4.3例，而安慰剂剂量为1.5例
BACKGROUND & AIMS: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase-C receptor that stimulates intestinal fluid secretion and transit and reduces pain in animal models. We assessed the safety and efficacy of a range of linaclotide doses in patients with chronic constipation. METHODS: We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 310 patients with chronic constipation. Patients were randomly assigned to groups given 75, 150, 300, or 600 mu g oral linaclotide or placebo once daily for 4 weeks. Symptom assessments included spontaneous bowel movements (SBMs), complete SBMs, stool consistency, straining, abdominal discomfort, and bloating. Severity of constipation, adequate relief of constipation, global relief of constipation, treatment satisfaction, quality of life, adverse events, clinical laboratory data, and electrocardiogram results were assessed. RESULTS: All doses of linaclotide improved the weekly rate of SBM (primary end point) compared with placebo; the increases in overall weekly number of SBMs from baseline were 2.6, 3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 mu g, respectively, compared with 1.5 for placebo (P