Impact of Emergency Department Probiotic Treatment of Pediatric Gastroenteritis

急诊科益生菌治疗小儿胃肠炎的影响

• 批准号: 8632268
• 负责人: Stephen Bradley Freedman
• 金额: $ 80.97万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-10 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632268
• 关键词: Abdomen; Absenteeism; Accident and Emergency department; Acute; Adverse effects; Adverse event; Affect; Age-Months; Applied Research; Caregivers; Cessation of life; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Clinical effectiveness; Collaborations; Consumption; Contracts; Cost Savings; Data; Dehydration; Developing Countries; Diarrhea; Disease; Double-Blind Method; Economic Burden; Economics; Effectiveness; Emergency Care; European; Family; Feces; Fever; Food Safety; Frequencies; Funding; Future; Gastroenteritis; Government Agencies; Growth; Guidelines; Health; Health Benefit; Health Care Visit; Healthcare; Healthcare Systems; Height; Hospitalization; Hospitalized Child; Immunologics; Infection; Infection Control; Institution; Intervention; Intestines; Knowledge; Lactobacillus casei rhamnosus; Life; Malnutrition; Manufacturer Name; Marketing; Medical; Methodology; Microbe; Modification; Morbidity - disease rate; Multicenter Studies; Outcome; Outcome Measure; Outpatients; Parents; Patients; Pediatric Hospitals; Physicians; Placebos; Policy Maker; Practice Guidelines; Prevention; Principal Investigator; Probiotics; Process; Prospective Studies; Public Health; Quality Control; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recommendation; Rehydrations; Reporting; Research; Resources; Role; Safety; Sample Size; Sampling; Serious Adverse Event; Severities; Societies; Solid; Solutions; Supportive care; Symptoms; Therapeutic Intervention; United States; United States Food and Drug Administration; Visit; Vomiting; Work; aged; authority; base; clinical practice; clinically relevant; cost; cost effectiveness; design; economic impact; improved; microbial; novel strategies; patient population; public health relevance; randomized placebo controlled trial; secondary infection; standard of care; symptom management; trend

DESCRIPTION (provided by applicant): Acute gastroenteritis (AGE) is a leading cause of malnutrition and death worldwide. In the US, close to 48 million people contract AGE and 128,000 are hospitalized each year . Episodes of AGE can result in substantial morbidity to children and their families. In addition, the costs to caregivers, the health-care system, and society are significant. At present, treatment options are limited and targeted at symptom management rather than disease modification. Probiotics - live microbial cultures which, when consumed in adequate amounts, confer documented health benefits - may be an ideal solution. They are hypothesized to work via a combination of direct microbiologic and immunologic mechanisms. Probiotics have shown promise in early clinical research in hospitalized children in developing countries. These early efforts are limited by small samples, outcomes lacking relevance to outpatients, poor methodology and absence of side effect reporting; thus, the potential role of probiotics remains poorly defined and practice guidelines do not endorse their use. There are current trends, however, that obligate an urgent assessment of these agents. First, probiotic manufacturers have embarked in aggressive public marketing strategies that make health claims that may not be supported by rigorous research, and the world-wide market for probiotic products is growing steadily (projected growth 2009-2014 12.6% for a total of US $32.6 billion/year). Second, government agencies (US FDA and European Food safety Authority (EFSA)) remain concerned about their value and safety. Third, some institutions are now recommending the use of probiotics based on potentially flawed or limited evidence. Fourth, parents of patients with AGE are often medicating their children without guidance from medical professionals. We are therefore concerned that probiotic consumption is increasing without solid evidence to support its use, which underscores the necessity to conduct a definitive trial without delay. Objectives - The overall objective of this multi-national randomized clinical trial is to determine if a specific probiotic agent, Lactobacillus rhamnosus GG(LGG), the most widely available, studied and regulated probiotic in the US, should routinely be administered to outpatient children who are suffering from AGE. The specific aims of this proposal are: (1) to determine the clinical effectiveness of LGG and (2) to determine the safety and side effect profile of LGG in children 3-48 months of age presenting to the Emergency Department (ED) with AGE. Study Setting & Design - The study will be conducted in 8 US pediatric emergency departments within the federally funded Pediatric Emergency Care Applied Research Network (PECARN). We will randomize 900 children to receive 5 days of a probiotic agent (LGG 1 x 1010 CFU twice a day) or placebo. The main outcome is the occurrence of moderate-severe disease as defined by the Modified Vesikari Score, a validated clinical severity score, which incorporates the frequency and duration of diarrhea, frequency and duration of vomiting, height of fever, need for future health-care visits and medical interventions provided. We will also assess the occurrence of adverse events and side effects related to the use of LGG. We will collect stool samples to conduct mechanism of action studies as well as economic data to conduct cost effectiveness analyses in the future. Impact - This study will directly inform clinica practice by providing the first definitive evidence to support recommendations for or against the routine use of probiotics in the treatment of pediatric AGE. In addition it will provide health-car practitioners and policy makers with (a) a clear picture on the potential side effects from probiotic use, and with the data collected (b) knowledge on the mechanism of action and (c) of the potential economic impact of probiotic use on health-care systems and society. Thus, the potential clinical and societal impacts of the proposed study are substantial and the results will guide the standard of care: if positive, guidelines will be able to endorse probiotic administratio with important positive consequences for the health of several million US children annually. Moreover, if beneficial the cost savings to the health-care system and society may be substantial. If the results are negative, a firm recommendation against the routine use of probiotics would be justified. Collaborators - This work is collaboration between leaders in multicenter and AGE research (Schnadower, Freedman, Tarr, Gorelick, Mahajan, Stanley, Roskind, Powell, O'Connel, Ruddy Chun, Levine and Casper) in prestigious Children's Hospitals within a federally funded multicenter network (PECARN) with a strong record in conducting high quality, high impact clinical trials.

描述（由申请人提供）：急性胃肠炎（AGE）是全球营养不良和死亡的主要原因。在美国，每年有近4800万人感染AGE，128，000人住院。老年痴呆症的发作可导致儿童及其家庭的大量发病。此外，护理人员、保健系统和社会的费用也很高。目前，治疗选择有限，并且针对症状管理而不是疾病改善。益生菌-活的微生物培养物，当消耗足够的量，赋予记录的健康益处-可能是一个理想的解决方案。它们被假设通过直接的微生物和免疫机制的组合起作用。益生菌在发展中国家住院儿童的早期临床研究中显示出了希望。这些早期的努力受到样本量小、结果与门诊患者缺乏相关性、方法学差和缺乏副作用报告的限制;因此，益生菌的潜在作用仍然定义不清，实践指南不支持其使用。然而，目前的趋势要求对这些物剂进行紧急评估。首先，益生菌制造商已经开始采取积极的公共营销策略，这些策略提出的健康声明可能没有得到严格研究的支持，益生菌产品的全球市场正在稳步增长（预计2009-2014年增长12.6%，总额为326亿美元/年）。其次，政府机构（美国FDA和欧洲食品安全局（EFSA））仍然关注其价值和安全性。第三，一些机构现在建议使用益生菌是基于潜在的缺陷或有限的证据。第四，AGE患者的父母经常在没有医疗专业人员指导的情况下给孩子用药。因此，我们感到关切的是，益生菌消费量正在增加，但没有确凿的证据支持其使用，这强调了立即进行明确试验的必要性。目的-这项多国随机临床试验的总体目标是确定是否应该对患有AGE的门诊儿童常规施用特定的益生菌制剂，鼠李糖乳杆菌GG（LGG），这是美国最广泛使用，研究和监管的益生菌。本提案的具体目的是：（1）确定LGG的临床有效性和（2）确定LGG在3-48个月大的AGE急诊科（艾德）就诊儿童中的安全性和副作用特征。研究设置和设计-该研究将在联邦资助的儿科急诊应用研究网络（PECARN）内的8个美国儿科急诊部门进行。我们将900名儿童随机接受为期5天的益生菌制剂（LGG 1 x 1010 CFU，每天两次）或安慰剂。主要结局是中重度疾病的发生，定义为改良Vesikari评分，一种经验证的临床严重程度评分，其中包括腹泻的频率和持续时间、呕吐的频率和持续时间、发热的高度、未来医疗访视的需要和提供的医疗干预。我们还将评估与使用LGG相关的不良事件和副作用的发生率。我们日后会收集粪便样本进行作用机制研究，以及收集经济数据进行成本效益分析。影响-这项研究将直接告知临床实践，提供第一个明确的证据，以支持或反对在儿科AGE治疗中常规使用益生菌的建议。此外，它将为保健从业者和决策者提供（a）益生菌使用的潜在副作用的清晰画面，以及收集的数据（B）关于作用机制的知识和（c）益生菌使用对保健系统和社会的潜在经济影响。因此，拟议研究的潜在临床和社会影响是巨大的，其结果将指导护理标准：如果是积极的，指南将能够支持益生菌管理，每年对数百万美国儿童的健康产生重要的积极影响。此外，如果有益的话，对保健系统和社会的成本节约可能是巨大的。如果结果是阴性的，则有理由坚决建议不要常规使用益生菌。合作者-这项工作是联邦资助的多中心网络（PECARN）内著名儿童医院的多中心和AGE研究领导者（Schnadower、Freedman、Tarr、Gorelick、Mahajan、Stanley、Roskind、Powell、O 'Connel、Ruddy Chun、Levine和Casper）之间的合作，在进行高质量、高影响力的临床试验方面拥有良好的记录。