Study of Acid Reflux in Asthma
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| ClinicalTrials.gov Identifier: NCT00069823 |
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Recruitment Status :
Completed
First Posted : October 3, 2003
Results First Posted : October 19, 2012
Last Update Posted : December 19, 2012
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Asthma Lung Diseases Lung Diseases, Obstructive | Drug: Esomeprazole Drug: Placebo proton pump inhibitor | Phase 3 |
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 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 |
| Actual Primary Completion Date : | May 2008 |
| Actual Study Completion Date : | May 2008 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Esomeprazole
Proton pump inhibitor of gastric acid
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Drug: Esomeprazole
Proton pump inhibitor 40 mg orally twice daily
Other Name: Nexium |
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Placebo Comparator: Placebo for esomeprazoe
Placebo
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Drug: Placebo proton pump inhibitor
Placebo proton pump inhibitor |
- 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
- Exacerbation Components: >=30% Drop in Peak Expiratory Flow on 2 Consecutive Days [ Time Frame: Baseline to 24 Weeks ]
- Exacerbation Components: Urgent Care Visit [ Time Frame: Measured at Month 6 ]
- Exacerbation Components: New Use of Oral Corticosteroids [ Time Frame: Baseline to 24 Weeks ]
- Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists [ Time Frame: Baseline to 24 Weeks ]
- 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.
- Night Awakening [ Time Frame: Baseline to 24 Weeks ]Rate of awakening at night because of asthma symptoms
- 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.
- 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
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Change in Number of Gastric Symptoms: No. of Symptoms [ Time Frame: Baseline to 24 Weeks ]Mean change
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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
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
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| Principal Investigator: | Robert Wise | Johns Hopkins University School of Public Health |
| Responsible Party: | Robert Wise, Professor, Johns Hopkins Bloomberg School of Public Health |
| ClinicalTrials.gov Identifier: | NCT00069823 |
| 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 |
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Asthma Lung Diseases Lung Diseases, Obstructive Bronchial Diseases Respiratory Tract Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity |
Immune System Diseases Esomeprazole Proton Pump Inhibitors Anti-Ulcer Agents Gastrointestinal Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |