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Trial record 1 of 1 for:    NCT00069823
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Study of Acid Reflux in Asthma

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ClinicalTrials.gov Identifier: NCT00069823
Recruitment Status : Completed
First Posted : October 3, 2003
Results First Posted : October 19, 2012
Last Update Posted : December 19, 2012
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Asthma Lung Diseases Lung Diseases, Obstructive Drug: Esomeprazole Drug: Placebo proton pump inhibitor Phase 3

Detailed Description:


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.


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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 403 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Study of Acid Reflux in Asthma
Study Start Date : September 2003
Primary Completion Date : May 2008
Study Completion Date : May 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma GERD
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Esomeprazole
Proton pump inhibitor of gastric acid
Drug: Esomeprazole
Proton pump inhibitor 40 mg orally twice daily
Other Name: Nexium
Placebo Comparator: Placebo for esomeprazoe
Drug: Placebo proton pump inhibitor
Placebo proton pump inhibitor

Outcome Measures

Primary Outcome Measures :
  1. Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion [ Time Frame: 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

Secondary Outcome Measures :
  1. Exacerbation Components: >=30% Drop in Peak Expiratory Flow on 2 Consecutive Days [ Time Frame: Baseline to 24 Weeks ]
  2. Exacerbation Components: Urgent Care Visit [ Time Frame: Measured at Month 6 ]
  3. Exacerbation Components: New Use of Oral Corticosteroids [ Time Frame: Baseline to 24 Weeks ]
  4. Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists [ Time Frame: Baseline to 24 Weeks ]
  5. Use of Rescue Medications [ Time Frame: Baseline to 24 Weeks ]
    Increase in the use of rescue meds by 4 or more uses on a particular day above the average uses during the run-in period.

  6. Night Awakening [ Time Frame: Baseline to 24 Weeks ]
    Rate of awakening at night because of asthma symptoms

  7. Pulmonary Function: Change in Prebronchodilator FEV1 [ Time Frame: Baseline to 24 Weeks ]
    Mean change in pre-bronchodilator FEV1 - forced expiratory volume in 1 second; a measure of pulmonary function. The treatment effect is the difference in the mean change in between the groups.

  8. Pulmonary Function: Change in Prebronchodilator Forced Vital Capacity [ Time Frame: Baseline to 24 Weeks ]
    Pulmonary function measured by mean change in Prebronchodilator forced vital capacity from baseline to 24 weeks

  9. Pulmonary Function: Change in Peak Flow Rate [ Time Frame: Baseline to 24 Weeks ]
    Mean change from baseline to 24 weeks in the peak flow rate - how forceful patient can blow out air

  10. Pulmonary Function: Change in PC20 [ Time Frame: Baseline to 24 Weeks ]
    Mean Change in the dose of methacholine that results in a 20% drop in FEV1

  11. Change in Juniper Asthma Control Score(JACQ) [ Time Frame: Baseline to 24 Weeks ]
    Mean change. Scores on the JACQ range from 0 to 6, with lower scores indicating better asthma control and 0.5 as the minimal clinically important difference.

  12. Change in Asthma Symptom Utility Index (ASUI) [ Time Frame: Baseline to 24 Weeks ]
    Mean change. Scores on the ASUI range from 0 to 1, with higher scores indicating less severe asthma.

  13. Change in the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ) [ Time Frame: Baseline to 24 Weeks ]
    Mean change. Scores on the Mini-Asthma Quality of Life Questionnaire (mini-AQLQ)range from 1 to 7, with higher scores indicating better quality of life and 0.5 as the minimal clinically important difference.

  14. Change in Medical Outcomes Study Short-Form 36 Score Quality of Life Score: Physical Component [ Time Frame: Baseline to 24 Weeks ]
    Mean change. Scores on the Medical Outcomes Study Short-Form 36 range from 1 to 100, with higher scores indicating better quality of life and 5 as the minimal clinically important difference.

  15. Change in Medical Outcomes Study Short-Form 36 Quality of Life Score: Mental Component [ Time Frame: Baseline to 24 Weeks ]
    Mean change. Scores on the Medical Outcomes Study Short-Form 36 range from 1 to 100, with higher scores indicating better quality of life and 5 as the minimal clinically important difference.

  16. Change in Gastric Symptoms: Gastroesophageal Reflux Disease Symptom Assessment Scale Score [ Time Frame: Baseline to 24 Weeks ]
    Mean change. The Gastroesophageal Reflux Disease Symptom Assessment Scale score ranges from 0 to 3, with lower numbers indicating less distress.

  17. Change in Number of Gastric Symptoms: No. of Symptoms [ Time Frame: Baseline to 24 Weeks ]
    Mean change

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00069823

  Hide Study Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California, San Diego
San Diego, California, United States, 92103
United States, Colorado
National Jewish Medical and Research Center
Denver, Colorado, United States, 80206
United States, Florida
Nemours Childrens Clinic
Jacksonville, Florida, United States, 32207
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University ACRC
Indianapolis, Indiana, United States, 46202
United States, Louisiana
LSUHSC Pulmonary Critical Care
New Orleans, Louisiana, United States, 70112
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Univ of MO Kansas City School of Medicine
Kansas City, Missouri, United States, 64108
Washington University School of Medicine
St. Louis, Missouri, United States, 63310-1093
United States, New York
North Shore-LIJ Medical Center
New Hyde Park, New York, United States, 11040
NYU School of Medicine
New York, New York, United States, 10016
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Thomas Jefferson Hospital Pulmonary Lab
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030-3411
United States, Vermont
Northern New England Consortium
Colchester, Vermont, United States, 05446
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
American Lung Association Asthma Clinical Research Centers
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Robert Wise Johns Hopkins University School of Public Health
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert Wise, Professor, Johns Hopkins Bloomberg School of Public Health
ClinicalTrials.gov Identifier: NCT00069823     History of Changes
Other Study ID Numbers: 157
U01HL072968 ( U.S. NIH Grant/Contract )
First Posted: October 3, 2003    Key Record Dates
Results First Posted: October 19, 2012
Last Update Posted: December 19, 2012
Last Verified: December 2012

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Gastroesophageal Reflux
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action