两种形式的洛哌丁胺-西甲硅油与一种益生菌酵母（布拉酵母菌）治疗成人急性腹泻的比较：一项随机非劣效性临床试验

Comparison of Two Forms of Loperamide-Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial.

作者信息

Cottrell Jeremy, Koenig Kerstin, Perfekt Roland, Hofmann Robert

机构信息

Medical Affairs, Johnson & Johnson Ltd, Foundation Park, Roxborough Way, Maidenhead, SL6 3UG, UK.

McNeil AB, PO Box 941, 251 09, Helsingborg, Sweden.

出版信息

Drugs R D. 2015 Dec;15(4):363-73. doi: 10.1007/s40268-015-0111-y.

DOI:10.1007/s40268-015-0111-y

PMID:26541878

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4662947/

Abstract

BACKGROUND

Acute diarrhoea is a frequent health problem in both travellers and residents that has a social and economic impact. This study compared the efficacy and tolerability of two loperamide-simeticone formulations and a Saccharomyces boulardii capsule as symptomatic treatment.

METHODS

This was a prospective, randomised, single (investigator)-blind, three-arm, parallel group, non-inferiority clinical trial in adult subjects with acute diarrhoea at clinics in Mexico and India, with allocation to a loperamide-simeticone 2/125 mg caplet or chewable tablet (maximum eight in 48 h) or S. boulardii (250 mg twice daily for 5 days).

OUTCOME MEASURES

The primary outcome measure was the number of unformed stools between 0 and 24 h following the initial dose of study medication (NUS 0-24). The secondary outcome measures were time to last unformed stool (TLUS), time to complete relief of diarrhoea (TCRD), time to complete relief of abdominal discomfort (TCRAD) and the subject's evaluation of treatment effectiveness. Follow-up endpoints at 7 days were feeling of complete wellness; stool passed since final study visit; and continued or recurrent diarrhoea.

SUBJECTS

In this study, 415 subjects were randomised to either a loperamide-simeticone caplet (n = 139), loperamide-simeticone chewable tablet (n = 139) or S. boulardii capsule (n = 137) and were included in the intention-to-treat analysis.

RESULTS

With regards to mean NUS 0-24, the loperamide-simeticone caplet was non-inferior to loperamide-simeticone tablets (3.4 vs. 3.3; one-sided 97.5 % confidence interval ≤0.5), with both significantly lower than S. boulardii (4.3; p < 0.001). The loperamide-simeticone groups had a shorter median TLUS [14.9 and 14.0 vs. 28.5 h (loperamide-simeticone caplet and chewable tablet groups, respectively, vs. S. boulardii); p < 0.001], TCRD (26.0 and 26.0 vs. 45.8 h; p < 0.001) and TCRAD (12.2 and 12.0 vs. 23.9 h; p < 0.005) than S. boulardii. Treatment effectiveness for overall illness, diarrhoea and abdominal discomfort relief was greater (p < 0.001) in the loperamide-simeticone groups than with S. boulardii. At 7-day follow-up most subjects reported passing stool at least once since the final study visit (loperamide-simeticone caplet 94.1 %, loperamide-simeticone chewable tablet 94.8 %, S. boulardii 97.0 %), did not experience continued or recurrent diarrhoea [loperamide-simeticone caplet 3.7 % (p < 0.03 vs. S. boulardii), loperamide-simeticone chewable tablet 3.7 %, S. boulardii 5.7 %] and felt completely well [loperamide-simeticone caplet 96.3 % (p < 0.02 vs. S. boulardii), loperamide-simeticone chewable tablet 96.3 % (p < 0.02 vs. S. boulardii), S. boulardii 88.6 %]. All treatments were well-tolerated with few adverse events.

CONCLUSIONS

The loperamide-simeticone caplet was non-inferior to the original loperamide-simeticone chewable tablet formulation; both formulations can be expected to demonstrate similar clinical efficacy in the relief of symptoms of acute diarrhoea. Both loperamide-simeticone formulations were superior to the S. boulardii capsule in the primary and secondary endpoints.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov identifier NCT00807326.

摘要

背景

急性腹泻是旅行者和居民中常见的健康问题，具有社会和经济影响。本研究比较了两种含洛哌丁胺 - 西甲硅油制剂和一种布拉酵母菌胶囊作为对症治疗的疗效和耐受性。

方法

这是一项前瞻性、随机、单（研究者）盲、三臂、平行组、非劣效性临床试验，研究对象为墨西哥和印度诊所中患有急性腹泻的成年受试者，随机分配至洛哌丁胺 - 西甲硅油2/125毫克胶囊或咀嚼片组（48小时内最多8片）或布拉酵母菌组（每日2次，每次250毫克，共5天）。

观察指标

主要观察指标为首次服用研究药物后0至24小时内不成形粪便的数量（NUS 0 - 24）。次要观察指标为最后一次不成形粪便的时间（TLUS）、腹泻完全缓解的时间（TCRD）、腹部不适完全缓解的时间（TCRAD）以及受试者对治疗效果的评估。7天的随访终点为完全康复的感觉；自最后一次研究访视后排出的粪便；以及持续性或复发性腹泻。

受试者

本研究中，415名受试者被随机分配至洛哌丁胺 - 西甲硅油胶囊组（n = 139）、洛哌丁胺 - 西甲硅油咀嚼片组（n = 139）或布拉酵母菌胶囊组（n = 137），并纳入意向性分析。

结果

关于平均NUS 0 - 24，洛哌丁胺 - 西甲硅油胶囊不劣于洛哌丁胺 - 西甲硅油片（3.4对3.3；单侧97.5%置信区间≤0.5），两者均显著低于布拉酵母菌组（4.3；p < 0.001）。洛哌丁胺 - 西甲硅油组的中位TLUS [分别为14.9和14.0小时，对比28.5小时（洛哌丁胺 - 西甲硅油胶囊组和咀嚼片组对比布拉酵母菌组）；p < 0.001]、TCRD（26.0和26.0小时对比45.8小时；p < 0.001）和TCRAD（12.2和12.0小时对比23.9小时；p < 0.005）均短于布拉酵母菌组。洛哌丁胺 - 西甲硅油组在总体疾病、腹泻和腹部不适缓解方面的治疗效果优于布拉酵母菌组（p < 0.001）。在7天随访时，大多数受试者报告自最后一次研究访视后至少排便一次（洛哌丁胺 - 西甲硅油胶囊组94.1%，洛哌丁胺 - 西甲硅油咀嚼片组94.8%；布拉酵母菌组97.0%），未出现持续性或复发性腹泻[洛哌丁胺 - 西甲硅油胶囊组3.7%（对比布拉酵母菌组p < 0.03），洛哌丁胺 - 西甲硅油咀嚼片组3.7%，布拉酵母菌组5.7%]，且感觉完全康复[洛哌丁胺 - 西甲硅油胶囊组96.3%（对比布拉酵母菌组p < 0.02），洛哌丁胺 - 西甲硅油咀嚼片组96.3%（对比布拉酵母菌组p < 0.02），布拉酵母菌组88.6%]。所有治疗耐受性良好，不良事件较少。