ORBEX: Primary Prevention of Asthma and Wheezing in Children-DCC

ORBEX：儿童哮喘和喘息的一级预防-DCC

• 批准号: 9487706
• 负责人: David T. Mauger
• 金额: $ 93.15万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-04 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9487706
• 关键词: Affect; Age; Allergic; Asthma; Biometry; Birth; Certification; Child; Childhood Asthma; Clinical; Clinical Trials; Collaborations; Communication; Data; Data Analyses; Data Collection; Data Coordinating Center; Data Quality; Data Reporting; Databases; Detection; Development; Disease; Double-Blind Method; Ensure; Equipment and supply inventories; Europe; Freeze Drying; Health Sciences; Hypersensitivity; Infant; Information Dissemination; Intervention; Label; Lead; Leadership; Life; Link; Masks; Medicine; Methodology; Monitor; Nursery Schools; Oral; Participant; Pathogenesis; Pharmaceutical Preparations; Placebos; Powder dose form; Predisposition; Prevention; Primary Prevention; Procedures; Process; Public Health; Publications; Quality of life; Randomized; Recurrence; Reporting; Research; Research Design; Respiratory physiology; Rhinovirus; Safety; Sample Size; Statistical Data Interpretation; Symptoms; System; Temperature; Testing; Time; Training; Virus Diseases; Wheezing; aged; airway remodeling; arm; asthma prevention; base; cohort; college; data integrity; data management; data warehouse; design; disability; disorder prevention; distributed data; epidemiology study; high risk; high risk infant; infancy; pathogenic bacteria; prevent; primary outcome; programs; public health relevance; quality assurance; remediation; respiratory; secondary outcome; tool; web site

 DESCRIPTION (provided by applicant): Major advances have been made in the last 25 years in our understanding of the pathogenesis of childhood asthma. Strong evidence from several birth cohorts indicates that most cases of persistent childhood asthma start in the first 3 years o life; that the disease first manifests as rhinovirus-positive wheezing lower respiratory illnesses (WLRI); and that it is strongly associated with early allergic sensitization. It has also been show that both the non-reversible changes in lung function associated with the more severe forms of childhood asthma and the initial signs of airway remodeling first appear during the preschool years. Recent epidemiological studies have shown that settings and dwellings that increase bacterial exposure in early life are protective against early WLRI and asthma, but the specific components responsible for this protection are unknown. Oral lyophilized, detoxified extracts of eight pathogenic bacteria (Bronchovaxom(r)) have been used empirically in Europe for the prevention of respiratory illnesses. Recent studies in preschoolers with asthma-like symptoms have suggested that Bronchovaxom has a strong effect in the prevention of WLRI. We propose the Oral Bacterial Extracts (ORBEX): Primary Prevention of Asthma and Wheezing in Children trial to test the hypothesis that Bronchovaxom, given to 6-18 month old children at high risk for asthma, can prevent the development of persistent wheezing by age 3.5-4.5 years. We will perform a randomized, double-blind, placebo-controlled, two arm clinical trial with a total of 1076 children with the following specific aims: 1. To evaluate if Bronchovaxom(r) given to high risk infants for 10 days monthly for two consecutive years can increase time to occurrence of the first WLRI episode during a third observation year after therapy (primary outcome) and whether the rate of WLRI will be reduced after therapy. 2. To determine if: Bronchovaxom(r) can reduce the time to occurrence and the rate of WRLI while the participants are receiving study drug during the initial two years of the study; can reduce the time to occurrence and rates of severe WLRI both during therapy and during the observation year after therapy; can reduce asthma-like symptoms using `episode-free days' during both the two years on study drug and during the observation year after therapy. 3. To evaluate the safety and tolerability of the sustained use of Bronchovaxom(r) in infancy through the preschool years.

 描述（由适用提供）：在过去的25年中，我们对儿童哮喘发病机理的理解已取得了重大进展。来自几个出生队列的有力证据表明，大多数持续性童年哮喘的病例在最初的三年o生命开始；该疾病首先表现为鼻病毒阳性下呼吸道疾病（WLRI）；并且它与早期过敏敏化密切相关。还表明，与更严重的儿童哮喘形式相关的肺功能的不可逆变化和气道重塑的初始迹象首先出现在学龄前年。最近的流行病学研究表明，在早期生命中增加细菌暴露的环境和住房受到了早期WLRI和哮喘的保护，但是负责此保护的特定组成部分是未知的。口服冻干的，八种致病细菌（支气管菌（R））的排毒提取物已在欧洲经验用于预防呼吸道疾病。最近对哮喘样症状的学龄前儿童的研究表明，支气管可索氏症对预防WLRI具有很强的作用。我们提出了口腔细菌提取物（ORBEX）：儿童试验中的哮喘和喘息的主要预防，以测试以下假设，即支气管可去了6-18个月大的儿童患哮喘的高风险，可以防止到3.5-4.5岁的持续下降。我们将执行一项随机，双盲，安慰剂对照，两次ARM临床试验，总共1076 具有以下具体目的的儿童：1。评估在治疗后第三个观察年（主要结果）中，连续两年给予高风险婴儿10天的支气管伏（R）是否会增加第一次WLRI发作的时间，以及治疗后的WLRI率是否会降低。 2。确定是否：支气管伏诺（R）可以减少在研究的最初两年中接受研究药物时的发生时间和WRLI的发生率；在治疗期间和治疗后的观察年中，都可以减少发生的时间和严重WLRI的发生率；在两年的研究药物和治疗后的观察年中，都可以使用“无情节日”来减少类似哮喘的症状。 3。评估在婴儿期到学龄前几年中持续使用支气管伏轴（R）的安全性和耐受性。