The Study of Acid Reflux in Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 403
- 试验地点
- 20
- 主要终点
- Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion
研究概览
简要总结
The purpose of this study is to determine if subjects with symptomatic asthma who are assigned to treatment with a proton pump inhibitor (PPI) drug such as Nexium have fewer asthma attacks than similar subjects assigned to placebo treatment.
详细描述
BACKGROUND:
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. Proton pump inhibitors are a relatively new class of medications that provide highly effective treatment for GERD and associated problems. This success has led many doctors to begin PPI treatment in their asthma patients in an attempt to achieve better asthma control.
DESIGN NARRATIVE:
The randomized, placebo-controlled trial will enroll 400 asthmatics, ages 18 or older, 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 twice a day, or matching placebo. The presence, severity, and temporal relationship of GERD to asthma symptoms will be documented with 24 hour ambulatory esophageal potential Hydrogen (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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The general goal of patient selection is to enroll patients for whom asthma physicians might prescribe GERD treatment, but where there is uncertainty whether it might be effective.
- •Age 18 or older
- •Physician diagnosed asthma
- •If amount of air expired in the first second during a forced expiratory maneuver (FEV1) is greater than or equal to 70% predicted normal pre-bronchodilator: demonstrate methacholine 20% from post-diluent baseline (PC20). PC20 less than 16 mg/ml during Visit 1
- •If FEV1 less than 70% and greater than or equal to 50% predicted normal pre-bronchodilator: demonstrate 12% reversibility during Visit 1 or within past 12 months
- •Currently on stable dose of daily inhaled steroids for asthma control, i.e., inhaled corticosteroid equivalent to 400 ug/day of fluticasone44 or greater for 8 weeks or longer
- •Poor asthma control: Either of the following; a score of 1.5 or greater on the Juniper Asthma Control Questionnaire; two or more episodes of asthma symptoms in the past 12 months with each episode requiring at least one of the following: an emergency department visit, unscheduled physician visit, prednisone course, hospitalization
- •Non-smoker for 6 months or longer
- •Less than 10 pack/year smoking history
排除标准
- •Surgery: Previous anti-reflux or peptic ulcer surgery
- •Pulmonary function: FEV1 less than 50% predicted normal pre-bronchodilator
- •GERD Symptoms: Severe reflux constituting a clinical indication for treatment with a PPI or H2 blocker, typically two or more episodes per week of heartburn requiring antacids
- •Other major chronic illnesses; conditions which in the judgment of the Study Physician would interfere with participation in the study, e.g., non-skin cancer, endocrine disease, coronary artery disease, congestive heart failure, stroke, severe hypertension, Type 1 insulin dependent diabetes mellitus, renal failure, liver disorders, immunodeficiency states, major neuropsychiatric disorder
- •Medication use: Anti-reflux medication (proton pump inhibitors or H2 blockers) within 1 month Theophylline, azoles, iron, anti-coagulants, insulin (for Type I diabetes), digitalis, any investigative drugs within 1 month
- •Drug allergy: Previous adverse effects from proton pump inhibitors or methacholine challenge
- •Females of childbearing potential: Pregnant or lactating, unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal)
- •Inability or unwillingness to provide consent
- •Inability to perform baseline measurements
- •Completion of less than 10 of the last 14 days of screening period diary entry
- •Inability to be contacted by telephone
- •Intention to move out of the area within 6 months
研究组 & 干预措施
Esomeprazole
Proton pump inhibitor of gastric acid
干预措施: Esomeprazole (Drug)
Placebo for esomeprazoe
Placebo
干预措施: Placebo proton pump inhibitor (Drug)
结局指标
主要结局
Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion
时间窗: Baseline to 24 Weeks
Episodes of poor asthma control was defined as any one of the following: 2 consecutive days with a drop in peak flow \>=30% of baseline; urgent care for asthma; or new use of oral corticosteroids for asthma
次要结局
- Exacerbation Components: >=30% Drop in Peak Expiratory Flow on 2 Consecutive Days(Baseline to 24 Weeks)
- Exacerbation Components: Urgent Care Visit(Measured at Month 6)
- Exacerbation Components: New Use of Oral Corticosteroids(Baseline to 24 Weeks)
- Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists(Baseline to 24 Weeks)
- Use of Rescue Medications(Baseline to 24 Weeks)
- Night Awakening(Baseline to 24 Weeks)
- Pulmonary Function: Change in Prebronchodilator FEV1(Baseline to 24 Weeks)
- Pulmonary Function: Change in Prebronchodilator Forced Vital Capacity(Baseline to 24 Weeks)
- Pulmonary Function: Change in Peak Flow Rate(Baseline to 24 Weeks)
- Pulmonary Function: Change in PC20(Baseline to 24 Weeks)
- Change in Juniper Asthma Control Score(JACQ)(Baseline to 24 Weeks)
- Change in Asthma Symptom Utility Index (ASUI)(Baseline to 24 Weeks)
- Change in the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ)(Baseline to 24 Weeks)
- Change in Medical Outcomes Study Short-Form 36 Score Quality of Life Score: Physical Component(Baseline to 24 Weeks)
- Change in Medical Outcomes Study Short-Form 36 Quality of Life Score: Mental Component(Baseline to 24 Weeks)
- Change in Gastric Symptoms: Gastroesophageal Reflux Disease Symptom Assessment Scale Score(Baseline to 24 Weeks)
- Change in Number of Gastric Symptoms: No. of Symptoms(Baseline to 24 Weeks)
研究者
Robert Wise
Professor
Johns Hopkins Bloomberg School of Public Health