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（由申请人提供）：在过去的25年里，我们对儿童哮喘发病机制的理解取得了重大进展。来自几个出生队列的有力证据表明，大多数持续性儿童哮喘病例始于生命的前3年;该疾病首先表现为鼻病毒阳性喘息性下呼吸道疾病（WLRI）;并且与早期过敏性致敏密切相关。研究还表明，与更严重形式的儿童哮喘相关的肺功能的不可逆变化和气道重塑的初始迹象都首次出现在学龄前。最近的流行病学研究表明，在生命早期增加细菌暴露的环境和住所对早期WLRI和哮喘具有保护作用，但负责这种保护的具体成分尚不清楚。在欧洲，八种病原菌（Bronchovaxom（r））的口服冻干解毒提取物已被经验性地用于预防呼吸道疾病。最近在有哮喘样症状的学龄前儿童中进行的研究表明，Bronchovaxom在预防WLRI方面具有很强的作用。我们提出了口服细菌提取物（ORBEX）：儿童哮喘和喘息的一级预防试验，以检验以下假设：给予6-18个月大的哮喘高危儿童Bronchovaxom，可以预防3.5-4.5岁的持续喘息的发展。我们将进行一项随机、双盲、安慰剂对照、两组临床试验，共纳入1076例受试者。 有以下具体目标的儿童：1.评估连续两年每月10天给予高危婴儿Bronchovaxom（r）是否可以增加治疗后第三个观察年内首次WLRI发作的发生时间（主要结局），以及治疗后WLRI的发生率是否会降低。2.确定是否：Bronchovaxom（r）可以在研究的最初两年期间，在受试者接受研究药物的情况下，缩短至发生WRLI的时间和WRLI的发生率;在治疗期间和治疗后的观察年期间，可以缩短至发生严重WLRI的时间和发生率;在研究药物的两年期间和治疗后的观察年期间，可以使用“无发作日”减少哮喘样症状。3.评价婴儿期至学龄前持续使用Bronchovaxom（r）的安全性和耐受性。