Clinical Trial of Acid Reflux Therapy in Asthma

描述(由申请人提供)： 胃食道反流(GERD)常见于哮喘控制不佳的哮喘患者，常无症状发生，可诱发支气管收缩。控制不佳的哮喘患者通常用抑制胃酸的药物治疗GERD，但这种治疗费用昂贵，而且这种治疗的益处尚未确定。这项建议的目的是进行一项多点随机临床试验，以检验使用质子泵抑制剂治疗GERD将减少哮喘控制不佳患者的恶化频率的假设。这项拟议的试验将招募400名年龄在18-60岁之间的哮喘患者，他们对吸入类固醇的哮喘控制较差，根据过度使用支气管扩张剂、夜间觉醒或频繁加重来定义。参与者将被随机分配到使用质子泵抑制剂埃索美拉唑(Nexium)40 mg Bid或匹配的安慰剂治疗。GERD的存在、严重程度和与哮喘症状的时间关系将通过24小时动态食道pH探头监测来记录，但参与者将被纳入，无论GERD的严重程度如何。主要的结果衡量标准是参与者在哮喘日记和访谈定义的6个月内哮喘恶化的比例。次要结果测量包括哮喘症状和控制评分、哮喘特有的和一般健康相关的生活质量、GERD症状、医疗保健使用、肺功能和呼吸道反应性。将进行预先指定的亚组分析，以确定是否有临床或人口学特征可以预测GERD治疗哮喘的益处。

DESCRIPTION (provided by applicant): Gastroesophageal reflux (GERD) is frequent in asthmatics with poor asthma control, often occurs without symptoms, and can induce bronchoconstriction. Poorly controlled asthmatics are often treated for GERD with drugs that suppress gastric acid, but this treatment is expensive and the benefit of such treatment is not established. The objective of this proposal is to conduct a multi-site randomized clinical trial testing the hypotheses that treatment of GERD with proton-pump inhibitors will reduce the frequency of exacerbations in patients with inadequately controlled asthma. The proposed trial will enroll 400 asthmatics, ages 18-60, who have poor asthma control on inhaled steroids, defined on the basis of excessive bronchodilator use, nocturnal awakenings, or frequent exacerbations. Participants will be randomly assigned to treatment with either a proton pump inhibitor, esomeprazole (Nexium) 40 mg BID, or matching placebo. The presence, severity, and temporal relationship of GERD to asthma symptoms will be documented with 24 hour ambulatory esophageal pH probe monitoring, but participants will be enrolled irrespective of the severity of GERD. The primary outcome measure is the proportion of participants who have exacerbations of asthma within a 6-month period defined by asthma diaries and interviews. Secondary outcome measures include asthma symptom and control scores, asthma-specific and generic health-related quality of life, GERD symptoms, health care use, pulmonary function, and airways reactivity. Pre-specified subgroup analyses will be conducted to determine if there are clinical or demographic characteristics that predict benefit from treatment of GERD in asthma.