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）是全世界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，其中 128,000 人住院治疗。 AGE 的发作可能导致儿童及其家庭大量发病。此外，护理人员、医疗保健系统和社会的成本也很高。目前，治疗选择有限，且针对的是症状管理而不是疾病缓解。益生菌——活的微生物培养物，当摄入足够量时，可带来有记录的健康益处——可能是一种理想的解决方案。假设它们通过直接微生物学和免疫学机制的结合发挥作用。益生菌在发展中国家住院儿童的早期临床研究中已显示出前景。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、方法不佳以及缺乏副作用报告的限制；因此，益生菌的潜在作用仍然不明确，实践指南也不认可其使用。然而，目前的趋势要求对这些药物进行紧急评估。首先，益生菌制造商已开始采取积极的公开营销策略，做出可能无法得到严格研究支持的健康声明，并且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%，总计 32.6 美元）十亿/年）。其次，政府机构（美国 FDA 和欧洲食品安全局（EFSA））仍然担心其价值和安全性。第三，一些机构现在基于可能存在缺陷或有限的证据推荐使用益生菌。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，我们担心益生菌的消费量正在增加，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常规对以下门诊儿童施用一种特定的益生菌剂：鼠李糖乳杆菌 GG(LGG)（美国最广泛使用、研究和监管的益生菌）。患有 AGE。该提案的具体目标是：(1) 确定 LGG 的临床有效性；(2) 确定 LGG 在 3-48 个月大的 AGE 急诊科 (ED) 儿童中的安全性和副作用概况。研究设置和设计 - 该研究将在联邦资助的儿科紧急护理应用研究网络 (PECARN) 内的 8 个美国儿科急诊科进行。我们将随机 900 名儿童接受为期 5 天的益生菌制剂（LGG 1 x 1010 CFU，每天两次）或安慰剂。主要结果是改良 Vesikari 评分所定义的中重度疾病的发生情况，这是一种经过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、发烧程度、未来医疗保健的需要提供探视和医疗干预。我们还将评估与使用 LGG 相关的不良事件和副作用的发生情况。未来我们将收集粪便样本进行作用机制研究以及经济数据进行成本效益分析。影响——这项研究将提供第一个明确的证据来支持支持或反对常规使用益生菌治疗儿科 AGE 的建议，从而直接为临床实践提供信息。此外，它还将为医疗保健从业者和政策制定者提供（a）关于使用益生菌的潜在副作用的清晰图景，以及收集到的数据（b）关于作用机制的知识和（c）潜在的经济利益。益生菌的使用对医疗保健系统和社会的影响。因此，拟议研究的潜在临床和社会影响是巨大的，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，医疗保健系统和社会的成本节省可能是巨大的。如果结果是否定的，则强烈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）之间的合作网络 (PECARN) 在开展高质量、高影响力的临床试验方面拥有良好的记录。