Clinical trial NCT00069823: Study of Acid Reflux in Asthma
Official title: The Study of Acid Reflux in Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lung Diseases
Lung Diseases, Obstructive
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: American Lung Association Asthma Clinical Research Centers
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2003-10-03
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion
timeFrame: Baseline to 24 Weeks
Secondary outcomes:
measure: Exacerbation Components: >=30% Drop in Peak Expiratory Flow on 2 Consecutive Days
timeFrame: Baseline to 24 Weeks
measure: Exacerbation Components: Urgent Care Visit
timeFrame: Measured at Month 6
measure: Exacerbation Components: New Use of Oral Corticosteroids
timeFrame: Baseline to 24 Weeks
measure: Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists
timeFrame: Baseline to 24 Weeks
measure: Use of Rescue Medications
timeFrame: Baseline to 24 Weeks
measure: Night Awakening
timeFrame: Baseline to 24 Weeks
measure: Pulmonary Function: Change in Prebronchodilator FEV1
timeFrame: Baseline to 24 Weeks
measure: Pulmonary Function: Change in Prebronchodilator Forced Vital Capacity
timeFrame: Baseline to 24 Weeks
measure: Pulmonary Function: Change in Peak Flow Rate
timeFrame: Baseline to 24 Weeks
measure: Pulmonary Function: Change in PC20
timeFrame: Baseline to 24 Weeks
measure: Change in Juniper Asthma Control Score(JACQ)
timeFrame: Baseline to 24 Weeks
measure: Change in Asthma Symptom Utility Index (ASUI)
timeFrame: Baseline to 24 Weeks
measure: Change in the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ)
timeFrame: Baseline to 24 Weeks
measure: Change in Medical Outcomes Study Short-Form 36 Score Quality of Life Score: Physical Component
timeFrame: Baseline to 24 Weeks
measure: Change in Medical Outcomes Study Short-Form 36 Quality of Life Score: Mental Component
timeFrame: Baseline to 24 Weeks
measure: Change in Gastric Symptoms: Gastroesophageal Reflux Disease Symptom Assessment Scale Score
timeFrame: Baseline to 24 Weeks
measure: Change in Number of Gastric Symptoms: No. of Symptoms
timeFrame: Baseline to 24 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University ACRC
state: Indiana
city: New Orleans
country: United States
facility: LSUHSC Pulmonary Critical Care
state: Louisiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Univ of MO Kansas City School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Hyde Park
country: United States
facility: North Shore-LIJ Medical Center
state: New York
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson Hospital Pulmonary Lab
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Colchester
country: United States
facility: Northern New England Consortium
state: Vermont
Study officials:
affiliation: Johns Hopkins University School of Public Health
name: Robert Wise
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bime C, Wei CY, Holbrook JT, Sockrider MM, Revicki DA, Wise RA. Asthma symptom utility index: reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients. J Allergy Clin Immunol. 2012 Nov;130(5):1078-84. doi: 10.1016/j.jaci.2012.07.058. Epub 2012 Sep 29.
citation: Bime C, Wei CY, Holbrook J, Smith LJ, Wise RA. Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. Prim Care Respir J. 2012 Dec;21(4):398-404. doi: 10.4104/pcrj.2012.00073.
citation: DiMango E, Holbrook JT, Simpson E, Reibman J, Richter J, Narula S, Prusakowski N, Mastronarde JG, Wise RA; American Lung Association Asthma Clinical Research Centers. Effects of asymptomatic proximal and distal gastroesophageal reflux on asthma severity. Am J Respir Crit Care Med. 2009 Nov 1;180(9):809-16. doi: 10.1164/rccm.200904-0625OC. Epub 2009 Aug 6.
citation: American Lung Association Asthma Clinical Research Centers; Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, Teague WG, Wise RA. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009 Apr 9;360(15):1487-99. doi: 10.1056/NEJMoa0806290.