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（年龄）是全球营养不良和死亡的主要原因。在美国，每年有近4800万人的合同年龄和128,000人住院。年龄发作可能会导致儿童及其家人的大量发病率。此外，照顾者，医疗保健系统和社会的成本很大。目前，治疗方案是有限的，并且针对症状管理，而不是疾病修饰。益生菌 - 活的微生物培养物，如果以足够的量消耗，则赋予有记录的健康益处 - 可能是理想的解决方案。假设它们通过直接微生物和免疫学机制的结合起作用。益生菌在早期的临床研究中表现出了发展中国家住院儿童的希望。这些早期的努力受小样本的限制，与门诊病人缺乏相关性的结果，方法不佳和缺乏副作用报告；因此，益生菌的潜在作用仍然很差，并且实践指南不认可其使用。但是，目前有一些趋势对这些代理人进行紧急评估。首先，益生菌制造商制定了积极的公共营销策略，这些策略使您的健康主张可能不受严格的研究支持，而益生菌产品的全球市场也在稳步增长（预计增长2009-2014 12.6％，总计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。第三，一些机构现在建议基于潜在有缺陷或有限的证据使用益生菌。第四，年龄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加药。因此，我们担心益生菌的消费量正在增加，而没有可靠的证据支持其使用，这突显了进行确定试验的必要性。目标 - 这项跨国随机临床试验的总体目标是确定特定的益生菌rhamnosus gg（LGG）是否应常规地给予患有年龄患者的门诊孩子的特定益生菌lamnosus gg（LGG）（LGG）。该提案的具体目的是：（1）确定LGG和（2）确定LGG的临床有效性，以确定年龄3-48个月大的儿童中LGG的安全性和副作用。研究设置与设计 - 该研究将在联邦资助的小儿急诊应用研究网络（PECARN）内的8个美国儿科急诊室进行。我们将使900名儿童随机接收5天的益生菌剂（每天两次LGG 1 x 1010 CFU）或安慰剂。主要结果是由改良的Vesikari评分定义的中度重度疾病（已验证的临床严重程度评分）所定义，该评分纳入了腹泻的频率和持续时间，呕吐的频率和持续时间，发烧的频率和持续时间，对未来的医疗保健访问的需求，提供了未来的医疗访问和医疗干预措施。我们还将评估与使用LGG有关的不良事件的发生和副作用。我们将收集粪便样本以进行行动研究机理以及未来进行经济数据以进行成本效益分析。影响 - 这项研究将通过提供第一个确定的证据来支持临床实践，以支持或反对常规使用益生菌治疗小儿年龄的建议。此外，它将为卫生车从业人员和政策制定者提供（a）对益生菌使用的潜在副作用以及收集的数据（b）对益生菌对卫生保健系统和社会的潜在经济影响的知识的清晰局面。因此，拟议的研究的潜在临床和社会影响是实质的，结果将指导护理标准：如果积极，指南将能够认可益生菌行政管理，对每年几百万美国儿童的健康产生重要的积极后果。此外，如果有利于为医疗保健系统和社会节省成本，那么可能会有大量资金。如果结果为负，则可以证明对益生菌常规使用的坚定建议是合理的。 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.