洛哌丁胺加西甲硅油与单独使用洛哌丁胺和单独使用西甲硅油治疗伴有气体相关腹部不适的急性腹泻的随机、双盲、安慰剂对照临床试验。

Randomized, double-blind, placebo-controlled clinical trial of loperamide plus simethicone versus loperamide alone and simethicone alone in the treatment of acute diarrhea with gas-related abdominal discomfort.

作者信息

Hanauer Stephen B, DuPont Herbert L, Cooper Kimberly M, Laudadio Charles

机构信息

Section of Gastroenterology and Nutrition, University of Chicago, Chicago, IL 60637, USA.

出版信息

Curr Med Res Opin. 2007 May;23(5):1033-43. doi: 10.1185/030079907x182176.

DOI:10.1185/030079907x182176

PMID:17519069

Abstract

OBJECTIVE

To compare efficacy and tolerability of a loperamide/simethicone (LOP/SIM) combination product with that of loperamide (LOP) alone, simethicone (SIM) alone, and placebo (PBO) for acute nonspecific diarrhea with gas-related abdominal discomfort.

RESEARCH DESIGN AND METHODS

In this multicenter, double-blind, 48-h study, patients were randomly assigned to receive two tablets, each containing either LOP/SIM 2 mg/125 mg (n = 121), LOP 2 mg (n = 120), SIM 125 mg (n = 123), or PBO (n = 121), followed by one tablet after each unformed stool, up to four tablets in any 24-h period. The primary outcome measures were time to last unformed stool and time to complete relief of gas-related abdominal discomfort. For time to last unformed stool, an unformed stool after a 24-h period of formed stools or no stools was considered a continuance of the original episode (stricter definition) or a new episode (alternate definition).

RESULTS

A total of 483 patients were included in the intent-to-treat analysis. The median time to last unformed stool for LOP/SIM (7.6 h) was significantly shorter than that of LOP (11.5 h), SIM (26.0 h), and PBO (29.4 h) (p < or = 0.0232 in comparison with survival curves) using the alternate definition; it was numerically but not significantly shorter than that of LOP (p = 0.0709) and significantly shorter than that of SIM and PBO (p = 0.0001) using the stricter definition. LOP/SIM-treated patients had a shorter time to complete relief of gas-related abdominal discomfort than patients who received either ingredient alone or placebo (all p = 0.0001). Few patients reported adverse events in the four treatment groups, none of which were serious in nature. Potential study limitations include the ability to generalize study results to the population at large, variability in total dose consumed, and subjectivity of patient diary data.

CONCLUSIONS

LOP/SIM was well-tolerated and more efficacious than LOP alone, SIM alone, or placebo for acute nonspecific diarrhea and gas-related abdominal discomfort.

摘要

目的

比较洛哌丁胺/西甲硅油（LOP/SIM）复方制剂与单用洛哌丁胺（LOP）、单用西甲硅油（SIM）及安慰剂（PBO）治疗伴有气体相关腹部不适的急性非特异性腹泻的疗效和耐受性。

研究设计与方法

在这项多中心、双盲、为期48小时的研究中，患者被随机分配接受两片药物，每片药物含LOP/SIM 2毫克/125毫克（n = 121）、LOP 2毫克（n = 120）、SIM 125毫克（n = 123）或PBO（n = 121），之后每次出现不成形大便后服用一片，24小时内最多服用四片。主要疗效指标为至最后一次不成形大便的时间以及至气体相关腹部不适完全缓解的时间。对于至最后一次不成形大便的时间，在出现24小时成形大便或无大便后出现的不成形大便被视为原发作的延续（更严格定义）或新发作（替代定义）。

结果

意向性分析共纳入483例患者。采用替代定义时，LOP/SIM组至最后一次不成形大便的中位时间（7.6小时）显著短于LOP组（11.5小时）、SIM组（26.0小时）和PBO组（29.4小时）（与生存曲线比较，p≤0.0232）；采用更严格定义时，其数值虽短于LOP组但无显著差异（p = 0.0709），且显著短于SIM组和PBO组（p = 0.0001）。与单用任一成分或安慰剂的患者相比，接受LOP/SIM治疗的患者至气体相关腹部不适完全缓解的时间更短（所有p = 0.0001）。四个治疗组中很少有患者报告不良事件，且均不严重。潜在的研究局限性包括研究结果推广至广大人群的能力有限、总服用剂量的变异性以及患者日记数据的主观性。