Study of Acid Reflux in Asthma
Study of Acid Reflux in Asthma
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.
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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