急诊科益生菌治疗小儿肠胃炎的影响：PROGUT（门诊肠胃炎治疗益生菌方案）随机对照试验的研究方案

Impact of emergency department probiotic treatment of pediatric gastroenteritis: study protocol for the PROGUT (Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment) randomized controlled trial.

作者信息

Freedman Stephen B, Williamson-Urquhart Sarah, Schuh Suzanne, Sherman Philip M, Farion Ken J, Gouin Serge, Willan Andrew R, Goeree Ron, Johnson David W, Black Karen, Schnadower David, Gorelick Marc H

机构信息

Sections of Paediatric Emergency Medicine and Gastroenterology, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada.

出版信息

Trials. 2014 May 14;15:170. doi: 10.1186/1745-6215-15-170.

DOI:10.1186/1745-6215-15-170

PMID:24885220

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4037747/

Abstract

BACKGROUND

The burden of acute gastroenteritis on children and their families continues to be enormous. Probiotics, defined as viable microbial preparations that have a beneficial effect on the health of the host, represent a rapidly expanding field. Although clinical trials in children with gastroenteritis have been performed, most have significant flaws, and guidelines do not consistently endorse their use.

METHODS/DESIGN: PROGUT is a randomized, placebo-controlled, double-blind, five-center, Canadian, emergency department trial. Children aged 3 months to 48 months who present between November 2013 and June 2017 with <72 hours of gastroenteritis symptoms will be assessed for eligibility. A total of 886 children will be randomized (1:1 allocation via an internet based, third party, randomization service) to receive 5 days of a combination probiotic agent (Lactobacillus rhamnosus and L. helveticus) or placebo. All participants, caregivers, and outcome assessors will be blinded to group assignment. The study includes three key outcomes: 1) clinical - the development of moderate to severe disease following an emergency department (ED) evaluation that employs a validated clinical score (Modified Vesikari Scale); 2) safety - side effect; and 3) mechanism - fecal secretory immunoglobulin A levels.

DISCUSSION

Definitive data are lacking to guide the clinical use of probiotics in children with acute gastroenteritis. Hence, probiotics are rarely prescribed by North American physicians. However, the following current trends obligate an urgent assessment: 1) probiotics are sold as food supplements, and manufacturers can encourage their use while their relevance has yet to be established; 2) North American and European government agencies remain concerned about their value and safety; 3) some institutions are now recommending the routine use of probiotics; and 4) parents of affected children are often providing probiotics. With probiotic consumption increasing in the absence of solid evidence, there is a need to conduct this definitive trial to overcome the limitations of prior work in this field.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT01853124; first registered 9 May 2013.

摘要

背景

急性肠胃炎给儿童及其家庭带来的负担依然巨大。益生菌是一类对宿主健康有益的活微生物制剂，这一领域正在迅速发展。虽然针对肠胃炎患儿开展了临床试验，但多数试验存在重大缺陷，且相关指南并未一致认可其使用。

方法/设计：PROGUT是一项在加拿大五个中心急诊科进行的随机、安慰剂对照、双盲试验。2013年11月至2017年6月期间出现肠胃炎症状且病程小于72小时的3个月至48个月大的儿童将接受资格评估。总共886名儿童将被随机分组（通过基于互联网的第三方随机服务按1:1分配），接受为期5天的复合益生菌制剂（鼠李糖乳杆菌和瑞士乳杆菌）或安慰剂治疗。所有参与者、护理人员和结果评估者都将对分组情况保持盲态。该研究包括三个关键结果：1）临床——采用经过验证的临床评分（改良维西卡里量表）在急诊科评估后出现中重度疾病；2）安全性——副作用；3）机制——粪便分泌型免疫球蛋白A水平。

讨论

缺乏确凿数据来指导益生菌在急性肠胃炎患儿中的临床应用。因此，北美医生很少开益生菌处方。然而，当前的以下趋势使得迫切需要进行评估：1）益生菌作为食品补充剂销售，制造商在其相关性尚未确立时就鼓励使用；2）北美和欧洲政府机构仍对其价值和安全性表示担忧；3）一些机构现在建议常规使用益生菌；4）患病儿童的家长经常给孩子服用益生菌。在缺乏确凿证据的情况下，益生菌的消费量不断增加，因此有必要开展这项确定性试验，以克服该领域先前研究的局限性。