权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Informative Clinical Studies in Asthma

哮喘信息丰富的临床研究

基本信息

批准号：
7283193
负责人：
Elliot Israel
金额：
$ 193.81万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-15 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7283193
关键词：
Accounting Achievement Adrenal Cortex Hormones Agonist American Asthma Breathing Caring Cessation of life Chronic Clinical Clinical Research Clinical Trials Code Combined Modality Therapy Cross-Over Studies Data Deterioration Disease Dose Double-Blind Method Education End Point Genes Genetic Polymorphism Glucocorticoid Receptor Guidelines Individual Investigation Israel Lead Leukotrienes Maintenance Measurement Morbidity - disease rate New Agents Numbers Outcome Patients Pharmaceutical Preparations Pharmacogenetics Placebo Control Prevention program Publishing Randomized Rate Recommendation Relative (related person)Research Salmeterol Savings Sputum Standards of Weights and Measures Symptoms Testing Time Toxic effect Variant Withdrawal Work base cohort cost dosage double-blind placebo controlled trial eosinophil experience improved leukotriene-C4 synthase placebo controlled study prevent promoter response tool

项目摘要

DESCRIPTION (provided by applicant): Despite significant advances in the treatment of asthma, optimal clinical therapy for patients with this increasingly common and potentially debilitating disease is still in flux. The first trial we propose for the Asthma Clinical Research Network (ACRN) emerges from expert-based guidelines recommending that individuals with mild-moderate persistent asthma symptoms, who comprise about 50% of patients requiring chronic asthma therapy, should be treated with controller agents such as inhaled corticosteroids (ICS). However, this may lead to over-treatment of many individuals who do not require such therapy. Data from a completed ACRN trial suggest that more than 60% of patients whose symptoms were controlled with continuous ICS did not experience exacerbations when discontinuing this medication. Our retrospective analysis of this trial suggests that changes in sputum eosinophils may identify 80% of the patients who can successfully discontinue inhaled corticosteroids. If confirmed, such a tool could prevent unnecessary treatment for a large cohort of asthmatics and result in an estimated $2 billion of savings per year. It could also identify patients requiring further therapy. We propose a double blind, placebo-controlled study to test this hypothesis. Our second trial focuses on patients with more severe disease, who account for a disproportionate amount of asthma-related morbidity. For patients whose symptoms persist in spite of treatment with ICS and a long-acting -agonist, alternatives are needed to the current recommendation of treatment with higher doses of ICS. Newer agents, such as leukotriene modifiers, may be beneficial for such patients. We will examine the effect of adding a leukotriene modifier to ICS and a long-acting -agonist vs. increasing the dosage of ICS with continuation of a long-acting -agonist among patients with moderate to severe asthma. Both trials will use asthma deteriorations as the primary outcome. In the second trial, we will also examine if the response to ICS therapy is associated with haplotypic variations in the gene coding for the glucocorticoid receptor and if the response to leukotriene modifiers is associated with polymorphisms of the LTC4 synthase promoter. This latter analysis may permit us to individualize therapy and therefore maximize benefit, decrease toxicity, and decrease cost.

描述(由申请人提供)：尽管哮喘的治疗取得了重大进展，但对这种日益常见并可能使人虚弱的疾病患者的最佳临床治疗仍在不断变化中。我们为哮喘临床研究网络(ACRN)提出的第一项试验来自基于专家的指南，该指南建议，具有轻度-中度持续性哮喘症状的个人，约占需要慢性哮喘治疗的患者的50%，应使用吸入性皮质类固醇(ICS)等控制剂进行治疗。然而，这可能会导致许多不需要这种治疗的人过度治疗。一项已完成的ACRN试验数据显示，在持续ICS控制了症状的患者中，超过60%的患者在停止使用这种药物时没有出现恶化。我们对这项试验的回顾分析表明，痰中嗜酸性粒细胞的变化可以确定80%的患者可以成功地停止吸入皮质类固醇。如果得到证实，这样的工具可以防止对大量哮喘患者进行不必要的治疗，并估计每年可节省20亿美元。它还可以识别需要进一步治疗的患者。我们提出了一项双盲、安慰剂对照研究来检验这一假设。我们的第二个试验关注的是患有更严重疾病的患者，他们在哮喘相关发病率中所占比例不成比例。对于那些在接受ICS和长效激动剂治疗后症状仍然存在的患者，需要替代目前推荐的高剂量ICS治疗。新的药物，如白三烯修饰剂，可能对这些患者有利。我们将研究在中到重度哮喘患者中，在ICS中加入白三烯调节剂和长效激动剂与增加ICS剂量并继续使用长效激动剂的效果。这两项试验都将哮喘恶化作为主要结果。在第二个试验中，我们还将检查对ICS治疗的反应是否与糖皮质激素受体基因编码的单倍型变异有关，以及对白三烯修饰剂的反应是否与LTC4合成酶启动子的多态有关。后一种分析可能允许我们个体化治疗，从而最大限度地提高效益，减少毒性，降低成本。