Clinical Trial of Acid Reflux Therapy in Asthma

描述（由申请人提供）： 胃食管反流（GERD）在哮喘控制不佳的哮喘患者中很常见，通常无症状发生，并可引起支气管收缩。 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。 本提案的目的是进行一项多中心随机临床试验，检验质子泵抑制剂治疗GERD将降低哮喘控制不佳患者的急性发作频率的假设。 该试验将招募400名哮喘患者，年龄在18-60岁之间，他们对吸入性类固醇的哮喘控制不佳，根据过度使用支气管扩张剂，夜间觉醒或频繁加重来定义。 受试者将被随机分配接受质子泵抑制剂埃索美拉唑（耐信）40 mg BID或匹配安慰剂治疗。 将通过24小时动态食管pH探头监测记录GERD的存在、严重程度和与哮喘症状的时间关系，但无论GERD的严重程度如何，都将入组受试者。 主要结果指标是在哮喘日记和访谈中定义的6个月内哮喘加重的参与者比例。 次要结局指标包括哮喘症状和控制评分、哮喘特异性和一般健康相关生活质量、GERD症状、医疗保健使用、肺功能和气道反应性。 将进行预先指定的亚组分析，以确定是否存在可预测哮喘GERD治疗获益的临床或人口统计学特征。

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.