Asthma
Conditions
Keywords
Asthma
Brief summary
The purpose of this study is to evaluate the effect of two different maintenance doses of Symbicort Maintenance And Reliever Therapy (SMART) in adult asthmatic patients. A 6 month treatment period
Interventions
DRUGBudesonide/formoterol
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients at out-patient clinics * \>18 years with a minimum of 6 months documented history of persistent asthma who have used inhaled glucocorticosteroids for at least one month and have a history of use in rapid-acting B2 agonists for symptom relief
Exclusion criteria
* Asthma exacerbation within the last 14 days prior to study start * subject aged \>40 years with a smoking history of \>10pack-years * subjects with chronic obstructive lung disease or other significant respiratory disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Severe Asthma Exacerbations Per Participant. | 6 months | Time to first severe asthma exacerbation, translated to mean number of severe asthma exacerbations per participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Severe Asthma Exacerbations That Led to Hospitalisation and/or Emergency Room Treatment. | 6 months. | A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. Number of events per participant |
| Total Number of Days Per Participant With Oral/Systemic Glucocorticosteroids During Severe Asthma Exacerbation | 6 months. | Total number of days with oral/systemic glucocorticosteroids during severe exacerbation calculated for each participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. |
| Mean Daily Number of Inhalations of As-needed Medication. | 4 weeks | The number of as-needed inhalations was measured 2 times during 2 weeks before 13 weeks and 26 weeks of treatment. |
| Fraction of Participants With Severe Asthma Exacerbation | 6 months. | The total number of severe asthma exacerbations was calculated for each participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. |
| Mean Overall Asthma Control Questionnaire (ACQ) Score | 6 months. | The ACQ5 was used. The lower value the better with a full range from 0=no impairment, 6= maximum impairment. Awakenings, morning symptoms, limitations, shortness of breath and wheeze. |
| The Mean Total Daily Dose of Steroids From Symbicort. | 4 weeks | The mean total daily dose of steroids from Symbicort was calculated as the sum of the maintenance dose and the as-needed dose. |
| Mean Cost Per Participant Per Country | 6 months | Mean cost is calculated for each country using participants from the whole study and country specific costs. Mean value for the whole study can not be calculated. |
| Percent of Participants With a Well Controlled Asthma Week. | 6 months. | The mean percent of participants fulfilling the criteria for a well controlled asthma week in each treatment. A well controlled asthma week is defined as a week with no exacerbations and no night-time awakenings due to asthma and a maximum of 2 days with symptoms and as-needed inhalation use. |
Countries
Belgium, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Netherlands, Norway, Russia, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
This was a 6-month, randomised, open label, parallel-group, active controlled, multinational study, in participants with uncontrolled/partly controlled asthma, who were symptomatic despite daily use of inhaled glucocorticosteroid (IGCS) with or without Long-Acting β2 agonist (LABA).
Participants by arm
| Arm | Count |
|---|---|
| Symbicort® SMART®) 1*2 1 inhalation of Symbicort 160µg/4.5µg twice daily plus as-needed. | 4,008 |
| Symbicort® SMART®) 2*2 2 inhalations of Symbicort 160µg/4.5µg twice daily plus as-needed. | 4,045 |
| Total | 8,053 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 70 | 93 |
| Overall Study | Incorrect Enrolment | 64 | 66 |
| Overall Study | Lost to Follow-up | 46 | 55 |
| Overall Study | Mis-Randomization of subject | 0 | 1 |
| Overall Study | Other | 22 | 22 |
| Overall Study | Safety Reason | 1 | 3 |
| Overall Study | Severe Non-Compliance to Protocol | 25 | 21 |
| Overall Study | Withdrawal by Subject | 81 | 79 |
Baseline characteristics
| Characteristic | Symbicort® SMART®) 1*2 | Symbicort® SMART®) 2*2 | Total |
|---|---|---|---|
| Age Continuous | 47.8 Years | 47.9 Years | 47.8 Years |
| Asthma control questionnaire (ACQ5) score at study entry ACQ5 score at study entry | 1.85 Units on a scale STANDARD_DEVIATION 0.98 | 1.86 Units on a scale STANDARD_DEVIATION 1.01 | 1.85 Units on a scale STANDARD_DEVIATION 0.99 |
| Exacerbations past 12 months before study start. | 1.47 Number of exacerbations per participant STANDARD_DEVIATION 2.42 | 1.42 Number of exacerbations per participant STANDARD_DEVIATION 2.42 | 1.45 Number of exacerbations per participant STANDARD_DEVIATION 2.42 |
| Inhaled glucocorticosteroids (IGCS) dose at study entry. IGCS dose at study entry | 1046 μg/day STANDARD_DEVIATION 595 | 1037 μg/day STANDARD_DEVIATION 575 | 1042 μg/day STANDARD_DEVIATION 585 |
| Participants with a well controlled asthma week at study entry. | 11.97 Percentage of participants | 11.77 Percentage of participants | 11.87 Percentage of participants |
| Pulmonary function test at baseline. Percent Included | 90.8 Percent of predicted normal value of PEF | 90.1 Percent of predicted normal value of PEF | 90.4 Percent of predicted normal value of PEF |
| Sex: Female, Male Female | 2483 Participants | 2512 Participants | 4995 Participants |
| Sex: Female, Male Male | 1525 Participants | 1533 Participants | 3058 Participants |
| Treatment with Long-Acting β2 agonist (LABA) at baseline. Number of participants using LABA at baseline. | 3108 Participants | 3118 Participants | 6226 Participants |
| Treatment with Long-Acting β2 agonist (LABA) at baseline. Number of participants without LABA at baseline. | 900 Participants | 927 Participants | 1827 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4,008 | 0 / 4,045 |
| serious Total, serious adverse events | 77 / 4,008 | 88 / 4,045 |
Outcome results
Primary
Number of Severe Asthma Exacerbations Per Participant.
Time to first severe asthma exacerbation, translated to mean number of severe asthma exacerbations per participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Number of Severe Asthma Exacerbations Per Participant. | 0.097 Severe exacerbations per participant | Full Range 0 |
| Symbicort® SMART®) 2*2 | Number of Severe Asthma Exacerbations Per Participant. | 0.080 Severe exacerbations per participant | Full Range 0 |
Secondary
Fraction of Participants With Severe Asthma Exacerbation
The total number of severe asthma exacerbations was calculated for each participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment.
Time frame: 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Fraction of Participants With Severe Asthma Exacerbation | 0.09686 Fraction of participants with event | 95% Confidence Interval 0.08528 |
| Symbicort® SMART®) 2*2 | Fraction of Participants With Severe Asthma Exacerbation | 0.07955 Fraction of participants with event | 95% Confidence Interval 0.06927 |
Secondary
Mean Cost Per Participant Per Country
Mean cost is calculated for each country using participants from the whole study and country specific costs. Mean value for the whole study can not be calculated.
Time frame: 6 months
Secondary
Mean Daily Number of Inhalations of As-needed Medication.
The number of as-needed inhalations was measured 2 times during 2 weeks before 13 weeks and 26 weeks of treatment.
Time frame: 4 weeks
Population: Inhalations of as-needed medication recorded by 3880 participants in the Symbicort SMART 1\*2 Reporting Group and recorded by 3881 participants in the Symbicort SMART 2\*2 Reporting Group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Mean Daily Number of Inhalations of As-needed Medication. | 0.897 Inhalations per day per participant | Full Range 0 |
| Symbicort® SMART®) 2*2 | Mean Daily Number of Inhalations of As-needed Medication. | 0.625 Inhalations per day per participant | Full Range 0 |
Secondary
Mean Overall Asthma Control Questionnaire (ACQ) Score
The ACQ5 was used. The lower value the better with a full range from 0=no impairment, 6= maximum impairment. Awakenings, morning symptoms, limitations, shortness of breath and wheeze.
Time frame: 6 months.
Population: Data for this measure recorded by 3709 participants in the Symbicort SMART 1\*2 Reporting Group and recorded by 3735 participants in the Symbicort SMART 2\*2 Reporting Group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Mean Overall Asthma Control Questionnaire (ACQ) Score | 1.18 Scores in a scale | Full Range 0 |
| Symbicort® SMART®) 2*2 | Mean Overall Asthma Control Questionnaire (ACQ) Score | 1.089 Scores in a scale | Full Range 0 |
Secondary
Percent of Participants With a Well Controlled Asthma Week.
The mean percent of participants fulfilling the criteria for a well controlled asthma week in each treatment. A well controlled asthma week is defined as a week with no exacerbations and no night-time awakenings due to asthma and a maximum of 2 days with symptoms and as-needed inhalation use.
Time frame: 6 months.
Population: Data for this measure recorded by 3714 participants in the Symbicort SMART 1\*2 Reporting Group and recorded by 3718 participants in the Symbicort SMART 2\*2 Reporting Group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Percent of Participants With a Well Controlled Asthma Week. | 43.69 Percentage of participants | Full Range 0 |
| Symbicort® SMART®) 2*2 | Percent of Participants With a Well Controlled Asthma Week. | 54.26 Percentage of participants | Full Range 0 |
Secondary
The Mean Total Daily Dose of Steroids From Symbicort.
The mean total daily dose of steroids from Symbicort was calculated as the sum of the maintenance dose and the as-needed dose.
Time frame: 4 weeks
Population: : Data for this measure recorded by 3874 participants in the Symbicort SMART 1\*2 Reporting Group and recorded by 3873 participants in the Symbicort SMART 2\*2 Reporting Group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | The Mean Total Daily Dose of Steroids From Symbicort. | 462.96 μg budesonide per day | Standard Deviation 179.1 |
| Symbicort® SMART®) 2*2 | The Mean Total Daily Dose of Steroids From Symbicort. | 736.58 μg budesonide per day | Standard Deviation 152.7 |
Secondary
Total Number of Days Per Participant With Oral/Systemic Glucocorticosteroids During Severe Asthma Exacerbation
Total number of days with oral/systemic glucocorticosteroids during severe exacerbation calculated for each participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment.
Time frame: 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Total Number of Days Per Participant With Oral/Systemic Glucocorticosteroids During Severe Asthma Exacerbation | 9.6 Days per participant | Standard Deviation 8.1 |
| Symbicort® SMART®) 2*2 | Total Number of Days Per Participant With Oral/Systemic Glucocorticosteroids During Severe Asthma Exacerbation | 9.1 Days per participant | Standard Deviation 5.5 |
Secondary
Total Number of Severe Asthma Exacerbations That Led to Hospitalisation and/or Emergency Room Treatment.
A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. Number of events per participant
Time frame: 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort® SMART®) 1*2 | Total Number of Severe Asthma Exacerbations That Led to Hospitalisation and/or Emergency Room Treatment. | 0.0120 Number of events per participant | Full Range 0 |
| Symbicort® SMART®) 2*2 | Total Number of Severe Asthma Exacerbations That Led to Hospitalisation and/or Emergency Room Treatment. | 0.0091 Number of events per participant | Full Range 0 |