Study of Acid Reflux in Asthma

• 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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  
• Exacerbation Components: Urgent Care Visit [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: No ]
  
• Exacerbation Components: New Use of Oral Corticosteroids [ Time Frame: Baseline to 24 Weeks ] [ Designated as safety issue: No ]
  
• Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists [ Time Frame: Baseline to 24 Weeks ] [ Designated as safety issue: No ]
  
• Use of Rescue Medications [ Time Frame: Baseline to 24 Weeks ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  Rate of awakening at night because of asthma symptoms
  
  
• Pulmonary Function: Change in Prebronchodilator FEV1 [ Time Frame: Baseline to 24 Weeks ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  Mean change
  
  

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.