Study of Acid Reflux in Asthma

Phase 3

Completed

• Conditions: Asthma; Lung Diseases, Obstructive; Lung Diseases
• Interventions: Drug: Placebo proton pump inhibitor; Drug: Esomeprazole

• Registration Number: NCT00069823
• Lead Sponsor: Johns Hopkins Bloomberg School of Public Health

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.

Study Timeline

• Study Start: 2003-09
• Study First Submitted: 2003-10-01
• Study First Submitted QC: 2003-10-02
• Study First Posted: 2003-10-03
• Primary Completion: 2008-05
• Study Completion: 2008-05
• Results First Submitted: 2010-05-14
• Results First Submitted QC: 2012-09-18
• Results First Posted: 2012-10-19
• Status Verified: 2012-12
• Last Update Submitted: 2012-12-17
• Last Update Posted: 2012-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 403

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo for esomeprazoe	Placebo proton pump inhibitor	Placebo
Esomeprazole	Esomeprazole	Proton pump inhibitor of gastric acid

Primary Outcome Measures

Name	Time	Method
Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion	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

Name	Time	Method
Pulmonary Function: Change in Prebronchodilator FEV1	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.
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	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.
Night Awakening	Baseline to 24 Weeks	Rate of awakening at night because of asthma symptoms
Pulmonary Function: Change in Prebronchodilator Forced Vital Capacity	Baseline to 24 Weeks	Pulmonary function measured by mean change in Prebronchodilator forced vital capacity from baseline to 24 weeks
Pulmonary Function: Change in Peak Flow Rate	Baseline to 24 Weeks	Mean change from baseline to 24 weeks in the peak flow rate - how forceful patient can blow out air
Pulmonary Function: Change in PC20	Baseline to 24 Weeks	Mean Change in the dose of methacholine that results in a 20% drop in FEV1
Change in Juniper Asthma Control Score(JACQ)	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.
Change in Asthma Symptom Utility Index (ASUI)	Baseline to 24 Weeks	Mean change. Scores on the ASUI range from 0 to 1, with higher scores indicating less severe asthma.
Change in the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ)	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.
Change in Medical Outcomes Study Short-Form 36 Score Quality of Life Score: Physical Component	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.
Change in Medical Outcomes Study Short-Form 36 Quality of Life Score: Mental Component	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.
Change in Gastric Symptoms: Gastroesophageal Reflux Disease Symptom Assessment Scale Score	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.
Change in Number of Gastric Symptoms: No. of Symptoms	Baseline to 24 Weeks	Mean change

Trial Locations

Locations (20)

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Northern New England Consortium; 🇺🇸 Colchester, Vermont, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Nemours Childrens Clinic; 🇺🇸 Jacksonville, Florida, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Indiana University ACRC; 🇺🇸 Indianapolis, Indiana, United States

NYU School of Medicine; 🇺🇸 New York, New York, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States

Thomas Jefferson Hospital Pulmonary Lab; 🇺🇸 Philadelphia, Pennsylvania, United States

North Shore-LIJ Medical Center; 🇺🇸 New Hyde Park, New York, United States

University of California, San Diego; 🇺🇸 San Diego, California, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

New York Medical College; 🇺🇸 Valhalla, New York, United States

National Jewish Medical and Research Center; 🇺🇸 Denver, Colorado, United States

LSUHSC Pulmonary Critical Care; 🇺🇸 New Orleans, Louisiana, United States

Univ of MO Kansas City School of Medicine; 🇺🇸 Kansas City, Missouri, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States