Asthma, GERD
Conditions
Keywords
Moderate to severe Asthma, Gastroesophageal Reflux Disease, esomeprazole, GERD
Brief summary
The purpose of this study is to determine whether treatment with esomeprazole for 6 months will improve asthma in adult patients with moderate to severe asthma and symptoms of gastroesophageal reflux disease.
Interventions
DRUGEsomeprazole
Esomeprazole 40 mg twice daily
DRUGPlacebo
Placebo twice daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adults with diagnosis of asthma since at least 6 months. * Symptoms of asthma during run-in. * At least 3 months history and present symptoms of 1 or more of the following: burning feeling behind breastbone, pain behind breastbone, acid taste in the mouth.
Exclusion criteria
* Patients with clinically relevant abnormalities. * Patients with a smoking history of ≥10 pack-year. * Patients who have had previous surgery on the esophagus or the stomach.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period). | Baseline to 6 months | Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. Results presented as a mean of all available data during the treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total | Baseline to 6 months | Participants must have both baseline and flow up measure to be included in analysis. Each morning and evening, the patient will be asked to record his/her asthma symptoms (sx) in the diary. The asthma sx scores during night- and daytime will be assessed by the patient according to the following scoring system: 0 = no asthma sx; 1 = you are aware of your asthma sx but can easily tolerate the sx; 2 = your asthma sx are causing you enough discomfort to cause problems with normal activities (or with sleep); 3 = you are unable to do your normal activities (or sleep) because of your asthma. The total symptom score is the sum of the night- and daytime scores. |
| Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months | Baseline to 6 months | This is the change in the average number of inhalations from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. Treatment mean calculated using the entire treatment period. |
| Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma | Baseline to 6 months | Change in percentage of nights with night-time awakening(s) due to asthma from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. |
| Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period. | From randomization (Visit 3) to visit 7. | Description: Changes in forced expiratory volume in 1 second (FEV1) from randomization (Visit 3) to the treatment period considered as mean value at Visits 4-7. Participants must have both baseline and follow up measure to be included in analysis. |
| Number of Patients With Severe Asthma Exacerbations. | Up to 6 months | — |
| Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute)) | Baseline to 6 months | Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. No dispersion measure available. |
| Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7 | Randomization (Visit 3) to Visit 7 | The RDQ questionnaire is used to assess six GI symptoms during the previous week (a burning feeling behind the breastbone, pain behind the breastbone, a burning feeling in the centre of the stomach, pain in the centre of the stomach, an acid taste in the mouth, unpleasant movement of material upwards from the stomach). Each symptom is given a frequency score on a six-point scale (from 0=did not have to 5=daily) and an intensity score on a six-point scale (from 0=did not have to 5=severe). Three domain scores are calculated by forming averages of the frequency and intensity scores of selected symptoms (heartburn: the first two symptoms; dyspepsia: the next two symptoms; regurgitation: the last two symptoms). The overall GERD score is calculated as the average of the hearburn and dyspepsia domain scores. The GERD score can thus range from 0 to 5. |
| Number of Severe Adverse Events | Up to 6 months | — |
| Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night | Baseline to 6 months | Participants must have both baseline and follow up measure to be included in analysis |
| Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day | Baseline to 6 months | Participants must have both baseline and follow up measure to be included in analysis |
| Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night | Baseline to 6 months | Participants must have both baseline and follow up measure to be included in analysis |
| Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7 | From randomization (Visit 3) to Visit 7 | The Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S))has been developed by and includes 32 questions in 4 domains: activity limitation, symptoms, emotional function, and exposure to environmental stimuli. It is used to measure the physical and emotional impact of the disease in the selected areas of life. Participants must have both baseline and follow up measure to be included in analysis.AQLQ(S) score based on a 7-point scale that ranged from 1 (worst quality of life) to 7 (best quality of life). |
Countries
Argentina, Bulgaria, Canada, Czechia, France, Germany, Hungary, Italy, Mexico, Poland, Portugal, Slovakia, Switzerland, United States
Participant flow
Pre-assignment details
Four randomized patients were excluded from the ITT analysis due to missing efficacy data (2 patients), no investigational product given (1 patient), and being unblinded by the investigator (1 patient). The patient who received no investigational product was excluded from the safety analysis and is not included in the Baseline Characteristics.
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole 40 mg Twice Daily Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily | 319 |
| Esomeprazole 40 mg Once Daily Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily | 313 |
| Placebo Placebo | 328 |
| Total | 960 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 | 4 |
| Overall Study | Lost to Follow-up | 0 | 2 | 3 |
| Overall Study | Multiple Reasons | 6 | 2 | 6 |
| Overall Study | Protocol Violation | 28 | 22 | 20 |
| Overall Study | Withdrawal by Subject | 10 | 7 | 12 |
Baseline characteristics
| Characteristic | Esomeprazole 40 mg Twice Daily | Esomeprazole 40 mg Once Daily | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 44.0 Years | 45.0 Years | 45.0 Years | 44.667 Years |
| Sex: Female, Male Female | 240.00 Participants | 240.00 Participants | 247.00 Participants | 727 Participants |
| Sex: Female, Male Male | 79.00 Participants | 73.00 Participants | 81.00 Participants | 233 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 319 | 44 / 313 | 55 / 328 |
| serious Total, serious adverse events | 7 / 319 | 5 / 313 | 5 / 328 |
Outcome results
Primary
Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period).
Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. Results presented as a mean of all available data during the treatment period.
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period). | 21.1891 L/minute | Standard Error 2.8689 |
| Esomeprazole 40 mg Once Daily | Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period). | 19.1847 L/minute | Standard Error 2.8422 |
| Placebo | Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period). | 15.6771 L/minute | Standard Error 2.8086 |
Secondary
Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7
The Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S))has been developed by and includes 32 questions in 4 domains: activity limitation, symptoms, emotional function, and exposure to environmental stimuli. It is used to measure the physical and emotional impact of the disease in the selected areas of life. Participants must have both baseline and follow up measure to be included in analysis.AQLQ(S) score based on a 7-point scale that ranged from 1 (worst quality of life) to 7 (best quality of life).
Time frame: From randomization (Visit 3) to Visit 7
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7 | 0.97 Scores on a scale | Standard Error 0.07 |
| Esomeprazole 40 mg Once Daily | Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7 | 0.83 Scores on a scale | Standard Error 0.07 |
| Placebo | Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7 | 0.55 Scores on a scale | Standard Error 0.07 |
Secondary
Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period.
Description: Changes in forced expiratory volume in 1 second (FEV1) from randomization (Visit 3) to the treatment period considered as mean value at Visits 4-7. Participants must have both baseline and follow up measure to be included in analysis.
Time frame: From randomization (Visit 3) to visit 7.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period. | 0.09 Liters | Standard Error 0.02 |
| Esomeprazole 40 mg Once Daily | Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period. | 0.07 Liters | Standard Error 0.02 |
| Placebo | Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period. | 0.02 Liters | Standard Error 0.02 |
Secondary
Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7
The RDQ questionnaire is used to assess six GI symptoms during the previous week (a burning feeling behind the breastbone, pain behind the breastbone, a burning feeling in the centre of the stomach, pain in the centre of the stomach, an acid taste in the mouth, unpleasant movement of material upwards from the stomach). Each symptom is given a frequency score on a six-point scale (from 0=did not have to 5=daily) and an intensity score on a six-point scale (from 0=did not have to 5=severe). Three domain scores are calculated by forming averages of the frequency and intensity scores of selected symptoms (heartburn: the first two symptoms; dyspepsia: the next two symptoms; regurgitation: the last two symptoms). The overall GERD score is calculated as the average of the hearburn and dyspepsia domain scores. The GERD score can thus range from 0 to 5.
Time frame: Randomization (Visit 3) to Visit 7
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7 | -1.95 Scores on a scale | Standard Error 0.07 |
| Esomeprazole 40 mg Once Daily | Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7 | -1.91 Scores on a scale | Standard Error 0.07 |
| Placebo | Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7 | -1.27 Scores on a scale | Standard Error 0.07 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day
Participants must have both baseline and follow up measure to be included in analysis
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day | -0.30 Scores on a scale | Standard Error 0.03 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day | -0.25 Scores on a scale | Standard Error 0.03 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day | -0.25 Scores on a scale | Standard Error 0.03 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night
Participants must have both baseline and follow up measure to be included in analysis
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night | -0.31 Scores on a scale | Standard Error 0.03 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night | -0.23 Scores on a scale | Standard Error 0.03 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night | -0.27 Scores on a scale | Standard Error 0.03 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total
Participants must have both baseline and flow up measure to be included in analysis. Each morning and evening, the patient will be asked to record his/her asthma symptoms (sx) in the diary. The asthma sx scores during night- and daytime will be assessed by the patient according to the following scoring system: 0 = no asthma sx; 1 = you are aware of your asthma sx but can easily tolerate the sx; 2 = your asthma sx are causing you enough discomfort to cause problems with normal activities (or with sleep); 3 = you are unable to do your normal activities (or sleep) because of your asthma. The total symptom score is the sum of the night- and daytime scores.
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total | -0.61 Scores on a scale | Standard Error 0.05721 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total | -0.47 Scores on a scale | Standard Error 0.05652 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total | -0.52 Scores on a scale | Standard Error 0.05609 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute))
Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. No dispersion measure available.
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute)) | 21.88 L/minute | Standard Error 2.89 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute)) | 18.37 L/minute | Standard Error 2.87 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute)) | 18.55 L/minute | Standard Error 2.83 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night
Participants must have both baseline and follow up measure to be included in analysis
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night | -0.30 Inhalations | Standard Error 0.05 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night | -0.27 Inhalations | Standard Error 0.05 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night | -0.29 Inhalations | Standard Error 0.04 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months
This is the change in the average number of inhalations from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. Treatment mean calculated using the entire treatment period.
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months | -0.77 Inhalations | Standard Error 0.1 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months | -0.73 Inhalations | Standard Error 0.1 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months | -0.68 Inhalations | Standard Error 0.1 |
Secondary
Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma
Change in percentage of nights with night-time awakening(s) due to asthma from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis.
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole 40 mg Twice Daily | Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma | -0.238 Percent of nights | Standard Error 0.018 |
| Esomeprazole 40 mg Once Daily | Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma | -0.219 Percent of nights | Standard Error 0.018 |
| Placebo | Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma | -0.223 Percent of nights | Standard Error 0.018 |
Secondary
Number of Patients With Severe Asthma Exacerbations.
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 mg Twice Daily | Number of Patients With Severe Asthma Exacerbations. | 33 Participants |
| Esomeprazole 40 mg Once Daily | Number of Patients With Severe Asthma Exacerbations. | 41 Participants |
| Placebo | Number of Patients With Severe Asthma Exacerbations. | 43 Participants |
Secondary
Number of Severe Adverse Events
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 mg Twice Daily | Number of Severe Adverse Events | 4 Events |
| Esomeprazole 40 mg Once Daily | Number of Severe Adverse Events | 5 Events |
| Placebo | Number of Severe Adverse Events | 9 Events |