Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE3
403 participants
INTERVENTIONAL
2003-09-30
2008-05-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Esomeprazole
Proton pump inhibitor of gastric acid
Esomeprazole
Proton pump inhibitor 40 mg orally twice daily
Placebo for esomeprazoe
Placebo
Placebo proton pump inhibitor
Placebo proton pump inhibitor
Interventions
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Esomeprazole
Proton pump inhibitor 40 mg orally twice daily
Placebo proton pump inhibitor
Placebo proton pump inhibitor
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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American Lung Association Asthma Clinical Research Centers
OTHER
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Johns Hopkins Bloomberg School of Public Health
OTHER
Responsible Party
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Robert Wise
Professor
Principal Investigators
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Robert Wise
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University School of Public Health
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California, San Diego
San Diego, California, United States
National Jewish Medical and Research Center
Denver, Colorado, United States
Nemours Childrens Clinic
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
Emory University
Atlanta, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Indiana University ACRC
Indianapolis, Indiana, United States
LSUHSC Pulmonary Critical Care
New Orleans, Louisiana, United States
University of Minnesota
Minneapolis, Minnesota, United States
Univ of MO Kansas City School of Medicine
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
North Shore-LIJ Medical Center
New Hyde Park, New York, United States
NYU School of Medicine
New York, New York, United States
New York Medical College
Valhalla, New York, United States
Duke University
Durham, North Carolina, United States
Ohio State University
Columbus, Ohio, United States
Thomas Jefferson Hospital Pulmonary Lab
Philadelphia, Pennsylvania, United States
Baylor College of Medicine
Houston, Texas, United States
Northern New England Consortium
Colchester, Vermont, United States
Countries
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References
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Kaminsky DA, He J, Henderson R, Dixon AE, Irvin CG, Mastronarde J, Smith LJ, Sugar EA, Wise RA, Holbrook JT. Bronchodilator response does not associate with asthma control or symptom burden among patients with poorly controlled asthma. Respir Med. 2023 Nov;218:107375. doi: 10.1016/j.rmed.2023.107375. Epub 2023 Aug 1.
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.
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.
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.
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.
Other Identifiers
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157
Identifier Type: -
Identifier Source: org_study_id