Study of Acid Reflux in Asthma

Asthma Clinical Trial

Official title:

The Study of Acid Reflux in Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00069823
• Other study ID #: 157
• Secondary ID: U01HL072968
• Status: Completed
• Phase: Phase 3
• First received: October 1, 2003
• Last updated: December 17, 2012
• Start date: September 2003
• Est. completion date: May 2008

Study information

• Verified date: December 2012
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Lung Diseases
• Lung Diseases, Obstructive

Intervention

Drug:
• Esomeprazole
Proton pump inhibitor 40 mg orally twice daily
• Placebo proton pump inhibitor
Placebo proton pump inhibitor

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Northern New England Consortium	Colchester	Vermont
United States	Ohio State University	Columbus	Ohio
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	Duke University	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University ACRC	Indianapolis	Indiana
United States	Nemours Childrens Clinic	Jacksonville	Florida
United States	Univ of MO Kansas City School of Medicine	Kansas City	Missouri
United States	University of Miami	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	North Shore-LIJ Medical Center	New Hyde Park	New York
United States	LSUHSC Pulmonary Critical Care	New Orleans	Louisiana
United States	NYU School of Medicine	New York	New York
United States	Thomas Jefferson Hospital Pulmonary Lab	Philadelphia	Pennsylvania
United States	University of California, San Diego	San Diego	California
United States	Washington University School of Medicine	St. Louis	Missouri
United States	New York Medical College	Valhalla	New York

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins Bloomberg School of Public Health	American Lung Association Asthma Clinical Research Centers, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion	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	Baseline to 24 Weeks	No
Secondary	Exacerbation Components: >=30% Drop in Peak Expiratory Flow on 2 Consecutive Days		Baseline to 24 Weeks	No
Secondary	Exacerbation Components: Urgent Care Visit		Measured at Month 6	No
Secondary	Exacerbation Components: New Use of Oral Corticosteroids		Baseline to 24 Weeks	No
Secondary	Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists		Baseline to 24 Weeks	No
Secondary	Use of Rescue Medications	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.	Baseline to 24 Weeks	No
Secondary	Night Awakening	Rate of awakening at night because of asthma symptoms	Baseline to 24 Weeks	No
Secondary	Pulmonary Function: Change in Prebronchodilator FEV1	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.	Baseline to 24 Weeks	No
Secondary	Pulmonary Function: Change in Prebronchodilator Forced Vital Capacity	Pulmonary function measured by mean change in Prebronchodilator forced vital capacity from baseline to 24 weeks	Baseline to 24 Weeks	No
Secondary	Pulmonary Function: Change in Peak Flow Rate	Mean change from baseline to 24 weeks in the peak flow rate - how forceful patient can blow out air	Baseline to 24 Weeks	No
Secondary	Pulmonary Function: Change in PC20	Mean Change in the dose of methacholine that results in a 20% drop in FEV1	Baseline to 24 Weeks	No
Secondary	Change in Juniper Asthma Control Score(JACQ)	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.	Baseline to 24 Weeks	No
Secondary	Change in Asthma Symptom Utility Index (ASUI)	Mean change. Scores on the ASUI range from 0 to 1, with higher scores indicating less severe asthma.	Baseline to 24 Weeks	No
Secondary	Change in the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ)	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.	Baseline to 24 Weeks	No
Secondary	Change in Medical Outcomes Study Short-Form 36 Score Quality of Life Score: Physical Component	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.	Baseline to 24 Weeks	No
Secondary	Change in Medical Outcomes Study Short-Form 36 Quality of Life Score: Mental Component	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.	Baseline to 24 Weeks	No
Secondary	Change in Gastric Symptoms: Gastroesophageal Reflux Disease Symptom Assessment Scale Score	Mean change. The Gastroesophageal Reflux Disease Symptom Assessment Scale score ranges from 0 to 3, with lower numbers indicating less distress.	Baseline to 24 Weeks	No
Secondary	Change in Number of Gastric Symptoms: No. of Symptoms	Mean change	Baseline to 24 Weeks	No