Asthma
Conditions
Keywords
asthma, exacerbation, persistent, bronchial hyperresponsiveness, mild, GINAII
Brief summary
An 18 months randomised double-blind study with two parallel arms with start dose of inhaled SERETIDE 50/100mcg BD or FLIXOTIDE 100mcg BD, Phase I is 6 months where the patient will be up-titrated until well controlled is achieved, After 6 months the treatment continues without changes during 9 months = PhaseII. The aim is to investigate and evaluate the assumption that the combination therapy with SERETIDE controls mild persistent asthma better than inhaled corticosteroids(FLIXOTIDE) alone.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Willing to give informed consent. * Males or females aged 18-70. * Able to understand and complete dairy cards. * Mild persistent asthma according to GINA. In addition, at randomisation subjects were required to have: 1. Day time symptoms more than once a week but not every day. 2. Night-time symptoms not more than once a week. 3. FEV1 \>80% predicted 4. PC20 \<8mg/mL
Exclusion criteria
* Change to regular asthma medication in 4-weeks prior to visit 1. * Use of oral, depot or parenteral corticosteroids within 8 weeks of visit 1. * Lower respiratory tract within 4 weeks of Visit 1 * Received investigational study drug within 4 weeks of visit * Smoking history of \>10 pack years of more. * Serious uncontrolled disease. * Medical conditions or medications known to affect the assessments or endpoints. * Evidence of alcohol or drug abuse. * Known pregnancy or planned pregnancy. * Known or suspected hypersensitivity to inhaled corticosteroids, beta-agonists or lactose. * Previous enrollment in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Each Arm With a Need for an Increase in Study Medication | Up to 18 months | During the first 6 months, when the asthma was unstable/uncontrolled, dose of Seretide (Sal/FP) was increased from 50/100 mcg in a stepwise fashion to 50/250 mcg and 50/500 mcg (if still unstable). Also, dose of Flixotide (FP only), was increased from 100 mcg to 250 mcg and 500 mcg (if still unstable). After the initial 6 months, the treatment was fixed without further changes. The total treatment period was 18 months. Number of participants in each arm with a need for an increase in study medication are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bronchial Hyper-responsiveness up to 18 Months | Up to 18 months | Data for this outcome measure was not collected. |
| Change in Bronchial Hyper-responsiveness From Baseline to 18 Months | Baseline (Day 0) to 18 months | Data for this outcome measure was not collected. |
| Number of Symptom-free Days and Nights Without Use of Rescue Medication | Up to 18 months | The rescue medications used for exacerbations included Ventoline Diskus® 200 mcg/dose inhalations as required and oral Prednisolone 25 mg per day for five days, and when necessary, ten days. Data for this outcome measure was not collected. |
| Number of Exacerbations: in Total and by Degree of Severity | Up to 18 months | Severe exacerbation: needed hospitalization/emergency unit visit. Moderate exacerbation: Needed oral cortico-steroid or adding inhaled Flixotide to maintenance study medicine; decrease in morning or evening peak expiratory flow (PEF) \> 30% during ≥ 2 following days from Baseline (Day 0). Mild exacerbation: any night symptoms ≥ 3 consecutive, or night symptoms ≥ 2 consecutive nights in case symptoms have been scored ≥ 2 during at least one night, Day symptoms scored ≥ 2 during ≥ 4 following days, or Day symptoms scored ≥ 3 during ≥ 3 following days, or Day symptoms scored ≥ 4 during ≥ 2 following days, or rescue medication use ≥ 2 occasions per day for ≥ 4 following days, or rescue medication use ≥ 3 occasions per day for ≥ 3 following days, or rescue medication use ≥ 4 occasions per day for ≥ 2 following days, or decrease in morning/evening PEF \>20% during ≥ 2 following days from Baseline (Day 0). Number of total exacerbations and severe, moderate and mild exacerbations are presented. |
| Time to Increase of Study Medication | Up to 6 months | Data for this outcome measure was not collected. |
Countries
Sweden
Participant flow
Recruitment details
This study was conducted at a single center with two sites in Sweden from May 2005 to July 2007. Seretide Diskus®, Flixotide® and Ventoline Diskus® are the registered products of GlaxoSmithKline.
Participants by arm
| Arm | Count |
|---|---|
| Seretide Eligible participants received a starting dose of 50/100 mcg Seretide (combination of Sal/FP) via Diskus inhaler, twice daily. During the first 6 months, when the asthma was unstable/uncontrolled, dose was increased in a stepwise fashion to 50/250 mcg and 50/500 mcg (if still unstable). After the initial 6 months, the treatment was fixed without further changes. The total treatment period was 18 months. | 50 |
| Flixotide Eligible participants received a starting dose of 100 mcg Flixotide (FP only) via Diskus inhaler, twice daily. During the first 6 months, when the asthma was unstable/uncontrolled, dose was increased in a stepwise fashion to 250 mcg and 500 mcg (if still unstable). After the initial 6 months, the treatment was fixed without further changes. The total treatment period was 18 months. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 3 | 1 |
| Overall Study | Pregnancy | 0 | 2 |
Baseline characteristics
| Characteristic | Flixotide | Total | Seretide |
|---|---|---|---|
| Age, Customized >=18 to 70 years | 50 Participants | 100 Participants | 50 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 100 Participants | 50 Participants |
| Sex: Female, Male Female | 31 Participants | 63 Participants | 32 Participants |
| Sex: Female, Male Male | 19 Participants | 37 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 48 / 50 | 47 / 50 |
| serious Total, serious adverse events | 3 / 50 | 0 / 50 |
Outcome results
Primary
Number of Participants in Each Arm With a Need for an Increase in Study Medication
During the first 6 months, when the asthma was unstable/uncontrolled, dose of Seretide (Sal/FP) was increased from 50/100 mcg in a stepwise fashion to 50/250 mcg and 50/500 mcg (if still unstable). Also, dose of Flixotide (FP only), was increased from 100 mcg to 250 mcg and 500 mcg (if still unstable). After the initial 6 months, the treatment was fixed without further changes. The total treatment period was 18 months. Number of participants in each arm with a need for an increase in study medication are presented.
Time frame: Up to 18 months
Population: Intent-to-Treat (ITT) Population which comprised of all participants who were randomized and received at least one dose of the study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seretide | Number of Participants in Each Arm With a Need for an Increase in Study Medication | 29 Participants |
| Flixotide | Number of Participants in Each Arm With a Need for an Increase in Study Medication | 29 Participants |
Secondary
Absolute Bronchial Hyper-responsiveness up to 18 Months
Data for this outcome measure was not collected.
Time frame: Up to 18 months
Population: Data for this outcome measure was not collected.
Secondary
Change in Bronchial Hyper-responsiveness From Baseline to 18 Months
Data for this outcome measure was not collected.
Time frame: Baseline (Day 0) to 18 months
Population: ITT population. Data for this outcome measure was not collected.
Secondary
Number of Exacerbations: in Total and by Degree of Severity
Severe exacerbation: needed hospitalization/emergency unit visit. Moderate exacerbation: Needed oral cortico-steroid or adding inhaled Flixotide to maintenance study medicine; decrease in morning or evening peak expiratory flow (PEF) \> 30% during ≥ 2 following days from Baseline (Day 0). Mild exacerbation: any night symptoms ≥ 3 consecutive, or night symptoms ≥ 2 consecutive nights in case symptoms have been scored ≥ 2 during at least one night, Day symptoms scored ≥ 2 during ≥ 4 following days, or Day symptoms scored ≥ 3 during ≥ 3 following days, or Day symptoms scored ≥ 4 during ≥ 2 following days, or rescue medication use ≥ 2 occasions per day for ≥ 4 following days, or rescue medication use ≥ 3 occasions per day for ≥ 3 following days, or rescue medication use ≥ 4 occasions per day for ≥ 2 following days, or decrease in morning/evening PEF \>20% during ≥ 2 following days from Baseline (Day 0). Number of total exacerbations and severe, moderate and mild exacerbations are presented.
Time frame: Up to 18 months
Population: ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Seretide | Number of Exacerbations: in Total and by Degree of Severity | Total exacerbations | 42 Exacerbations |
| Seretide | Number of Exacerbations: in Total and by Degree of Severity | Severe exacerbations | 0 Exacerbations |
| Seretide | Number of Exacerbations: in Total and by Degree of Severity | Moderate exacerbations | 12 Exacerbations |
| Seretide | Number of Exacerbations: in Total and by Degree of Severity | Mild exacerbations | 30 Exacerbations |
| Flixotide | Number of Exacerbations: in Total and by Degree of Severity | Mild exacerbations | 52 Exacerbations |
| Flixotide | Number of Exacerbations: in Total and by Degree of Severity | Total exacerbations | 74 Exacerbations |
| Flixotide | Number of Exacerbations: in Total and by Degree of Severity | Moderate exacerbations | 21 Exacerbations |
| Flixotide | Number of Exacerbations: in Total and by Degree of Severity | Severe exacerbations | 1 Exacerbations |
Secondary
Number of Symptom-free Days and Nights Without Use of Rescue Medication
The rescue medications used for exacerbations included Ventoline Diskus® 200 mcg/dose inhalations as required and oral Prednisolone 25 mg per day for five days, and when necessary, ten days. Data for this outcome measure was not collected.
Time frame: Up to 18 months
Population: ITT population. Data for this outcome measure was not collected.
Secondary
Time to Increase of Study Medication
Data for this outcome measure was not collected.
Time frame: Up to 6 months
Population: ITT population. Data for this outcome measure was not collected.