Study of Acid Reflux in Asthma

• ClinicalTrials.gov Identifier: NCT00069823
• Recruitment Status: Completed
• First Posted: October 3, 2003
• Results First Posted: October 19, 2012
• Last Update Posted: December 19, 2012
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: American Lung Association Asthma Clinical Research Centers; National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Robert Wise, Johns Hopkins Bloomberg School of Public Health

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Asthma; Lung Diseases; Lung Diseases, Obstructive
• Interventions: Drug: Esomeprazole; Drug: Placebo proton pump inhibitor
• Enrollment: 403

Participant Flow

Recruitment Details	The planned enrollment was for 400 participants, 403 participants actually were enrolled and randomized in the trial. It is not uncommon for clinical trials not to exactly meet the sample size stated in the protocol.
Pre-assignment Details

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Period Title: Overall Study
Started	199 [1]	203 [1]
Completed	193	200
Not Completed	6	3
Reason Not Completed
Did not have follow-up diary cards	6	3
[1] The design was for 200 participants per group, the study did not exactly meet the design.

Baseline Characteristics

Arm/Group Title		Placebo	Esomeprazole	Total
Arm/Group Description		40 mg of placebo twice daily	40 mg of esomeprazole twice daily	Total of all reporting groups
Overall Number of Baseline Participants		199	203	402
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	199 participants	203 participants	402 participants
		42 (13)	42 (13)	42 (13)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	199 participants	203 participants	402 participants
	Female	143 71.9%	130 64.0%	273 67.9%
	Male	56 28.1%	73 36.0%	129 32.1%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
White		103	102	205
Black		73	79	152
Hispanic		17	18	35
Other		6	4	10
		[1] Measure Description: Race or ethnic group was self-reported.
Asthma medication use; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
Inhaled corticosteroids		50	44	94
Combination of fluticasone and salmeterol		149	159	308
Body-mass index >=30 [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
BMI >=30		107	102	209
BMI <30		92	101	193
		[1] Measure Description: The body-mass index is the weight in kilograms divided by the square of the height in meters.
Conditions other than asthma [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
Gastroesophageal reflux disease		38	21	59
No GER reported		161	182	343
		[1] Measure Description: These conditions were self-reported.
Former smoker; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
Former Smoker		40	31	71
Never smoked		159	172	331
Health Care Visits [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
Health care visit for asthma exacerbation		126	109	235
No visit		73	94	167
		[1] Measure Description: Unscheduled health care visit for asthma in previous year
Pulmonary function; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
Participants with 20% post-diluent measurement		92	83	175
20% from post-diluent contraindicated		102	117	219
Missing		5	3	8
potential Hydrogen (pH) monitoring [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	199 participants	203 participants	402 participants
Positive result		62	61	123
Negative result		89	92	181
Missing result		48	50	98
		[1] Measure Description: Results of ambulatory measure of esophageal potential Hydrogen (pH) for 16 to 24 hours. Test were considered positive if pH was less than 4 for more than 5.8% of the total tiem, 8.2% of upright time, or 3.5% of supine time.
%Predicted amount of air expired in the first second during a forced expiration pre broncho-dilator [1]; Mean (Standard Deviation); Unit of measure: Percent
	Number Analyzed	199 participants	203 participants	402 participants
		78 (15)	76 (16)	77 (16)
		[1] Measure Description: Percent of the predicted value for the amount of air expired in the first second during a forced expiratory maneuver (FEV1) based on gender, age and ethnicity that the measured value is.
Age of onset of asthma; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	199 participants	203 participants	402 participants
		17 (17)	17 (16)	17 (16)
Age of participants; Mean (Standard Deviation); Unit of measure: Years	Number Analyzed	199 participants	203 participants	402 participants
at randomization		42 (13)	42 (13)	42 (13)
at onset of asthma		17 (17)	17 (16)	17 (16)
Asthma scores [1]; Mean (Standard Deviation); Unit of measure: Score	Number Analyzed	199 participants	203 participants	402 participants
ACQ		1.9 (0.8)	1.8 (0.8)	1.8 (0.8)
ASUI		0.74 (0.18)	0.76 (0.15)	0.75 (0.15)
mini asthma quality of life questionnaire		4.7 (1.2)	4.7 (1.2)	4.7 (1.2)
		[1] Measure Description: Asthma Control Score (ACS)ranges from 0 to 6, lower scores indicating better asthma control and 0.5 as the minimal clinically important difference; Asthma Symptom Utility Index (ASUI) score ranges from 0 to 1, higher scores indicating less severe asthma; Mini-Asthma Quality of Life Questionnaire (mini-AQLQ) score range from 1 to 7, higher scores indicating better quality of life and 0.5 as the minimal clinically important difference.
Percent change in FEV1 after bronchodilator [1]; Mean (Standard Deviation); Unit of measure: Percent change
	Number Analyzed	199 participants	203 participants	402 participants
		10 (10)	11 (16)	11 (13)
		[1] Measure Description: The percent difference in FEV1 before and after using a bronchodilator (albuterol) divided by the value before bronchodilation.

Outcome Measures

1. Primary Outcome

Title	Episodes of Poor Asthma Control (EPAC) From Diary Cards, According to Definition That Did Not Include Use of Beta-agonists as a Criterion
Description	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
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person year
	2.3	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	The rates of EPACs were compared using incidence-rate ratios (IRR). IRR and P value were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.66
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.5
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Exacerbation Components: >=30% Drop in Peak Expiratory Flow on 2 Consecutive Days
Description	[Not Specified]
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person-year
	1.7	2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	Rates were compared with incidence-rate ratios (IRR). The IRR and P values were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.35
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.8 to 2.0
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Exacerbation Components: Urgent Care Visit
Description	[Not Specified]
Time Frame	Measured at Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person-year
	0.6	0.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	Rates were compared with incidence-rate ratios (IRR). The IRR and P values were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.79
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.5
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Exacerbation Components: New Use of Oral Corticosteroids
Description	[Not Specified]
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person year
	0.6	0.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	Rates were compared with incidence-rate ratios (IRR). The IRR and P values were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.62
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.3
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Asthma Episodes, According to Definition That Included Increased Use of Beta-agonists
Description	[Not Specified]
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person-year
	4.4	4.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	Rates were compared with incidence-rate ratios (IRR). The IRR and P values were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.87
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.3
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Use of Rescue Medications
Description	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.
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person-year
	3.0	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	Incidence-rate ratios and P values were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.62
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	0.9
	Confidence Interval	95%; 0.7 to 1.3
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Night Awakening
Description	Rate of awakening at night because of asthma symptoms
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	193	200
Measure Type: Number; Unit of Measure: events per person-year
	30	28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	Incidence-rate ratios and P values were estimated with the use of negative binomial regression models with robust variance estimates.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.70
	Comments	P values are for the treatment effect of esomeprazole as compared with placebo.
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Incidence-Rate Ratio
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.4
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Pulmonary Function: Change in Prebronchodilator FEV1
Description	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.
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

The analyses are based on data from 191 participants in the placebo group and 201 in the esomeprazole group, with the following exception: 41 participants in the placebo group and 37 in the esomeprazole group for measurement of 20% post-diluent baseline (PC20).

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: liters
	-0.02; (-0.06 to 0.01)	0.00; (-0.04 to 0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	The treatment effect is the mean change in the Esomeprazole group - mean change in placebo group
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.36
	Comments	P values were calculated with the use of linear regression.
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.08
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.03
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group, e.g. 0.00 - (-0.02) = -0.03 (rounding)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: liters
	-0.03; (-0.06 to 0.01)	0.00; (-0.04 to 0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.30
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.09
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.03
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: liters/min
	3.2; (-3.5 to 9.9)	9.2; (1.8 to 16.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.24
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95%; -4.0 to 16.0
	Parameter Dispersion	Type: Standard Error of the mean; Value: 5.1
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	41	37
Mean (95% Confidence Interval); Unit of Measure: mg/ml
	1.5; (0.2 to 2.9)	0.3; (-1.4 to 0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.04
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.8
	Confidence Interval	95%; -3.6 to -0.1
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change in Juniper Asthma Control Score(JACQ)
Description	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.
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: score
	-0.3; (-0.4 to -0.2)	-0.2; (-0.3 to -0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.11
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.2
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.1
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: score
	0.05; (0.03 to 0.07)	0.02; (0.01 to 0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.11
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.05 to -0.02
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.01
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

14. Secondary Outcome

Title	Change in the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ)
Description	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.
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: score
	0.3; (0.2 to 0.4)	0.3; (0.2 to 0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.33
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.1
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.1
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

15. Secondary Outcome

Title	Change in Medical Outcomes Study Short-Form 36 Score Quality of Life Score: Physical Component
Description	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.
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: score
	2.0; (1.1 to 2.9)	1.1; (0.3 to 1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.16
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.4
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.6
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

16. Secondary Outcome

Title	Change in Medical Outcomes Study Short-Form 36 Quality of Life Score: Mental Component
Description	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.
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: score
	0.0; (-1.8 to 1.1)	0.4; (-0.5 to 1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.56
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 2.2
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.78
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: score
	-0.17; (-0.21 to -0.12)	-0.16; (-0.20 to -0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.76
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.07
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.03
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

18. Secondary Outcome

Title	Change in Number of Gastric Symptoms: No. of Symptoms
Description	Mean change
Time Frame	Baseline to 24 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Esomeprazole
Arm/Group Description:	40 mg of placebo twice daily	40 mg of esomeprazole twice daily
Overall Number of Participants Analyzed	191	201
Mean (95% Confidence Interval); Unit of Measure: symptoms
	-1.7; (-2.1 to -1.3)	-1.9; (-2.3 to -1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Esomeprazole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.39
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.3
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.3
	Estimation Comments	Treatment effect is the difference in mean change in the esomeprazole group minus the mean change in the placebo group

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo		Esomeprazole
Arm/Group Description	40 mg of placebo twice daily		40 mg of esomeprazole twice daily
All-Cause Mortality
	Placebo		Esomeprazole
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Placebo		Esomeprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/199 (8.04%)		10/203 (4.93%)
Cardiac disorders
Hospitalization for possible cardiac ischemia †	2/193 (1.04%)	2	0/203 (0.00%)	0
General disorders
Hospitalization or emergency department visit for surgery, trauma, or other acute illness *	9/193 (4.66%)	10	5/203 (2.46%)	6
Pregnancy, puerperium and perinatal conditions
Pregnancy †	1/143 (0.70%)	1	0/130 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation requiring hospitalization *	4/193 (2.07%)	4	3/203 (1.48%)	3
Pneumonia †	0/193 (0.00%)	0	1/203 (0.49%)	1
Death from complications after surgery for endobronchial tumor *	0/193 (0.00%)	0	1/203 (0.49%)	1
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo		Esomeprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/199 (0.00%)		0/203 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Ellen Brown
• Organization: Johns Hopkins University
• Phone: 443-287-3170
• EMail: ala-acrc@jhsph.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bime C, Wei CY, Holbrook JT, Sockrider MM, Revicki DA, Wise RA. Asthma symptom utility index: reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients. J Allergy Clin Immunol. 2012 Nov;130(5):1078-84. doi: 10.1016/j.jaci.2012.07.058. Epub 2012 Sep 29.

Bime C, Wei CY, Holbrook J, Smith LJ, Wise RA. Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. Prim Care Respir J. 2012 Dec;21(4):398-404. doi: 10.4104/pcrj.2012.00073.

DiMango E, Holbrook JT, Simpson E, Reibman J, Richter J, Narula S, Prusakowski N, Mastronarde JG, Wise RA; American Lung Association Asthma Clinical Research Centers. Effects of asymptomatic proximal and distal gastroesophageal reflux on asthma severity. Am J Respir Crit Care Med. 2009 Nov 1;180(9):809-16. doi: 10.1164/rccm.200904-0625OC. Epub 2009 Aug 6.

American Lung Association Asthma Clinical Research Centers; Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, Teague WG, Wise RA. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009 Apr 9;360(15):1487-99. doi: 10.1056/NEJMoa0806290.

• Responsible Party: Robert Wise, Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00069823
• Other Study ID Numbers: 157; U01HL072968 ( U.S. NIH Grant/Contract )
• First Submitted: October 1, 2003
• First Posted: October 3, 2003
• Results First Submitted: May 14, 2010
• Results First Posted: October 19, 2012
• Last Update Posted: December 19, 2012