Back to resultsTreatment Of Symptomatic Asthma In Children
Primary Purpose
Asthma
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
fluticasone propionate 2 x 100 mcg
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring salmeterol/fluticasone combination, Asthma, bronchial hyperresponsiveness, Children, symptom control
Eligibility Criteria
Inclusion criteria: Male or female subjects aged 6-12 years (inclusive) A female is eligible to enter and participate in the study if she is: of non-child-bearing potential; OR of child-bearing potential, but not lactating and pregnant. She declares that it is not probable that she will become pregnant during the study (a pregnancy test can be performed at the investigators discretion) Subjects with a documented history of asthma for at least 6 months Subjects with a documented history of BHR within 12 months prior to inclusion or BHR on visit 1 (PD20 methacholine < 150 mcg or an equivalence for histamine) Subjects who have received BDP, budesonide up to 100-200 mcg bd or fluticasone propionate at a dose of up to 125 mcg bd for at least 4 weeks before the start of the run-in period. Subjects who are able to use a electronic peakflow /FEV1 meter (PIKO-1) Subjects who have a normal length SD score between -2SD and +2SD Subjects who are able to use a Diskus inhaler Subjects who are able to perform reproducible lung function tests at visit 1 (variation FEV1 < 5% between the two best measurements) Subjects and their guardians, who have given written informed consent to participate in the study Subjects or their parent/ guardian who are able to understand and complete a DRC. The DRC may be completed by a parent/guardian if the subject is unable to do this him/ herself Subjects able to use Ventolin on an 'as required for symptoms' basis Exclusion criteria: Subjects who have been hospitalised for their asthma within 4 weeks of visit 1 Subjects who had an acute upper respiratory tract infection within 2 weeks or a lower respiratory tract infection within 4 weeks prior to visit 1 Subjects who received oral, parental or depot corticosteroids within 4 weeks prior to visit 1 Subjects who have a known respiratory disorder other than asthma and/or systemic/thoracic abnormalities which influence normal lung function Subjects with a disorder that affects growth (e.g. Turner's syndrome) Subjects who have received any investigational drugs within 4 weeks of visit 1 Subjects with a known or suspected hypersensitivity to inhaled steroids, β2-agonists or lactose Subjects who use any medication that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole Subjects who concurrently participate in another clinical study Subjects who have previously been randomised in this trial
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Other
Arm Label
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
fluticasone propionate 2 x 100 mcg
Arm Description
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
fluticasone propionate 2 x 100 mcg
Outcomes
Primary Outcome Measures
Percentage of Symptom-free Days During the Last 10 Weeks of the Treatment Period
Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary.
Secondary Outcome Measures
Percentage of Symptom-free Days During the Entire Treatment Period
Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary
Mean Change From Baseline in Percentage Predicted Forced Expiratory Volume in One Second (FEV1) at Week 26
Change from Baseline was calculated as the Week 26 value minus the Baseline value. The percentage predicted FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath and is corrected for the FEV1 value corresponding with the same age.
Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 26
Change from Baseline was calculated as the Week 26 value minus the Baseline value. Forced vital capacity is defined as the maximum volume of air that can be forcibly expired from the lungs and is calculated by use of spirometry. The spirometry test is performed by using a device called a spirometer, which measures the amount of air one can blow out maximally. Generally, the participant is asked to take the deepest breath they can, and then exhale into the sensor as hard as possible, for as long as possible. The test is normally repeated three times to ensure reproducibility.
Mean Change From Baseline in Midexpiratory Flow (MEF 50) at Week 26
Change from Baseline was calculated as the Week 26 value minus the Baseline value. MEF 50 is defined as maximum expiratory flow rate at 50% of vital capacity. Vital capacity is the maximum amount of air that a person can expel from the lungs after first filling the lungs to their maximum extent. Midexpiratory flow was calculated by use of spirometry. The test is normally repeated at least three times in order to ensure reproducibility.
Geometric Means of Nitric Oxide (NO) at Week 26
Geometric mean values of NO at week 26 were compared using ANCOVA with adjustment for baseline value of NO, age, gender and center. Analysis of covariance (ANCOVA) is a general linear model with one continuous outcome variable (quantitative) and one or more factor variables.
Percent Change From Baseline in RINT Measurements at Week 26
Change from Baseline was calculated as the Week 26 value minus the Baseline value. Interrupter respiratory resistance (RINT) measurements were calculated by a combined analysis for relation between change from baseline and occurrence of the endpoint. RINT is a technique that is used for evaluating lung function in poorly collaborating patients (e.g., small children). The measurement is performed during tidal breathing (normal breathing) instead of during maximal expiration, as is done by a spirometry test.
Number of Asthma Exacerbations Per Treatment Group at Week 26
An exacerbation is defined as a worsening of the asthma complaints (commonly referred to as an asthma attack) and is reported by the participant experiencing the event. An exacerbation was verified by the use of asthma rescue medication.
Mean Change From Baseline in Provocation Dose (PD20) Causing a 20% Fall in FEV1 at Week 26
PD20 was calculated by using increasing dosages of methacholine. The dosage that caused a 20% fall in FEV1 was used for analysis. The presented data are ratios (month 6/Baseline) of geometric mean PD20 values.
Bronchial Hyperresponsiveness With PD20 AMP in Selected Centres
Bronchial hyperresponsiveness with PD20 AMP in selected centres was not analyzed, as this outcome measure was removed in a protocol amendment.
Daily FEV1 and PEF Via the Electronic Peak Flow/FEV1 Meter (PIKO-1)
Daily FEV1 and PEF via the electronic pea kflow/FEV1 meter (PIKO-1) was not assessed because data from the peak flow meters could not be used for analysis.
Frequency of Asthma Exacerbations (Discriminated on Severity)
The frequency of asthma exacerbations (discriminated on severity) was not analyzed because of the low overall frequency.
Cumulative Number of Symptom-free Weeks Until the End of Treatment
This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.
Weekly Percentage of Participants With 'Good Controlled Weeks' and 'Maximal Controlled Weeks'
This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.
Time to Asthma Control, Defined as the Time to First 'Good Controlled Week' or 'Maximum Controlled Week'
This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00197106
Brief Title
Treatment Of Symptomatic Asthma In Children
Official Title
A Multicentre, Randomised, Double-blind, Parallel Group Study to Compare the Efficacy and Safety of Salmeterol/Fluticasone Propionate Combination Product (Seretide®) 50/100 mcg With Fluticasone Propionate (Flixotide® ) 200 mcg, Both Delivered Twice Daily Via the DISKUS Inhaler, in the Treatment of Children Aged 6-12 Years With Symptomatic Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
This study is being conducted to investigate whether in childhood salmeterol/ fluticasone propionate 50/100 bd delivered via the Diskus® inhaler and fluticasone propionate 200 mcg bd delivered via the Diskus® inhaler are non- inferior in terms of symptom control. Additionally we aim to show that salmeterol/ fluticasone propionate 50/100 bd is at least as good in terms of lung function improvement and bronchial hyperreactivity and enables a steroid-sparing management of asthma in children.
Detailed Description
A multicentre, randomised, double blind, parallel group study to compare the efficacy and safety of Salmeterol/Fluticasone propionate combination product (Seretide®) 50/100mcg with Fluticasone propionate (Flixotide®) 200mcg, both delivered twice daily via the DISKUS inhaler, in the treatment of children aged 6-12 years with symptomatic asthma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
salmeterol/fluticasone combination, Asthma, bronchial hyperresponsiveness, Children, symptom control
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
176 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
Arm Type
Active Comparator
Arm Description
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
Arm Title
fluticasone propionate 2 x 100 mcg
Arm Type
Other
Arm Description
fluticasone propionate 2 x 100 mcg
Intervention Type
Drug
Intervention Name(s)
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
Intervention Description
comparator
Intervention Type
Drug
Intervention Name(s)
fluticasone propionate 2 x 100 mcg
Other Intervention Name(s)
Salmeterol/ fluticasone propionate Diskus® inhaler 50/100 mcg
Intervention Description
comparator
Primary Outcome Measure Information:
Title
Percentage of Symptom-free Days During the Last 10 Weeks of the Treatment Period
Description
Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary.
Time Frame
Last 10 weeks of the treatment period (Weeks 16-26)
Secondary Outcome Measure Information:
Title
Percentage of Symptom-free Days During the Entire Treatment Period
Description
Asthma symptom-free days are defined as days (24 hour period) with no symptoms, as recorded in the participant's diary
Time Frame
Baseline to Week 26
Title
Mean Change From Baseline in Percentage Predicted Forced Expiratory Volume in One Second (FEV1) at Week 26
Description
Change from Baseline was calculated as the Week 26 value minus the Baseline value. The percentage predicted FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath and is corrected for the FEV1 value corresponding with the same age.
Time Frame
Baseline and Week 26
Title
Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 26
Description
Change from Baseline was calculated as the Week 26 value minus the Baseline value. Forced vital capacity is defined as the maximum volume of air that can be forcibly expired from the lungs and is calculated by use of spirometry. The spirometry test is performed by using a device called a spirometer, which measures the amount of air one can blow out maximally. Generally, the participant is asked to take the deepest breath they can, and then exhale into the sensor as hard as possible, for as long as possible. The test is normally repeated three times to ensure reproducibility.
Time Frame
Baseline and Week 26
Title
Mean Change From Baseline in Midexpiratory Flow (MEF 50) at Week 26
Description
Change from Baseline was calculated as the Week 26 value minus the Baseline value. MEF 50 is defined as maximum expiratory flow rate at 50% of vital capacity. Vital capacity is the maximum amount of air that a person can expel from the lungs after first filling the lungs to their maximum extent. Midexpiratory flow was calculated by use of spirometry. The test is normally repeated at least three times in order to ensure reproducibility.
Time Frame
Baseline and Week 26
Title
Geometric Means of Nitric Oxide (NO) at Week 26
Description
Geometric mean values of NO at week 26 were compared using ANCOVA with adjustment for baseline value of NO, age, gender and center. Analysis of covariance (ANCOVA) is a general linear model with one continuous outcome variable (quantitative) and one or more factor variables.
Time Frame
Baseline and Week 26
Title
Percent Change From Baseline in RINT Measurements at Week 26
Description
Change from Baseline was calculated as the Week 26 value minus the Baseline value. Interrupter respiratory resistance (RINT) measurements were calculated by a combined analysis for relation between change from baseline and occurrence of the endpoint. RINT is a technique that is used for evaluating lung function in poorly collaborating patients (e.g., small children). The measurement is performed during tidal breathing (normal breathing) instead of during maximal expiration, as is done by a spirometry test.
Time Frame
Baseline and Week 26
Title
Number of Asthma Exacerbations Per Treatment Group at Week 26
Description
An exacerbation is defined as a worsening of the asthma complaints (commonly referred to as an asthma attack) and is reported by the participant experiencing the event. An exacerbation was verified by the use of asthma rescue medication.
Time Frame
Week 26
Title
Mean Change From Baseline in Provocation Dose (PD20) Causing a 20% Fall in FEV1 at Week 26
Description
PD20 was calculated by using increasing dosages of methacholine. The dosage that caused a 20% fall in FEV1 was used for analysis. The presented data are ratios (month 6/Baseline) of geometric mean PD20 values.
Time Frame
Baseline and Week 26
Title
Bronchial Hyperresponsiveness With PD20 AMP in Selected Centres
Description
Bronchial hyperresponsiveness with PD20 AMP in selected centres was not analyzed, as this outcome measure was removed in a protocol amendment.
Time Frame
26 weeks
Title
Daily FEV1 and PEF Via the Electronic Peak Flow/FEV1 Meter (PIKO-1)
Description
Daily FEV1 and PEF via the electronic pea kflow/FEV1 meter (PIKO-1) was not assessed because data from the peak flow meters could not be used for analysis.
Time Frame
26 weeks
Title
Frequency of Asthma Exacerbations (Discriminated on Severity)
Description
The frequency of asthma exacerbations (discriminated on severity) was not analyzed because of the low overall frequency.
Time Frame
26 weeks
Title
Cumulative Number of Symptom-free Weeks Until the End of Treatment
Description
This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.
Time Frame
26 weeks
Title
Weekly Percentage of Participants With 'Good Controlled Weeks' and 'Maximal Controlled Weeks'
Description
This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.
Time Frame
26 weeks
Title
Time to Asthma Control, Defined as the Time to First 'Good Controlled Week' or 'Maximum Controlled Week'
Description
This outcome measure was not analyzed due to different insights after protocol finalization; it has become clear that the definition of good and maximal controlled weeks is not very distinctive and can therefore actually not be used.
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Male or female subjects aged 6-12 years (inclusive)
A female is eligible to enter and participate in the study if she is:
of non-child-bearing potential; OR of child-bearing potential, but not lactating and pregnant. She declares that it is not probable that she will become pregnant during the study (a pregnancy test can be performed at the investigators discretion)
Subjects with a documented history of asthma for at least 6 months
Subjects with a documented history of BHR within 12 months prior to inclusion or BHR on visit 1 (PD20 methacholine < 150 mcg or an equivalence for histamine)
Subjects who have received BDP, budesonide up to 100-200 mcg bd or fluticasone propionate at a dose of up to 125 mcg bd for at least 4 weeks before the start of the run-in period.
Subjects who are able to use a electronic peakflow /FEV1 meter (PIKO-1)
Subjects who have a normal length SD score between -2SD and +2SD
Subjects who are able to use a Diskus inhaler
Subjects who are able to perform reproducible lung function tests at visit 1 (variation FEV1 < 5% between the two best measurements)
Subjects and their guardians, who have given written informed consent to participate in the study
Subjects or their parent/ guardian who are able to understand and complete a DRC. The DRC may be completed by a parent/guardian if the subject is unable to do this him/ herself
Subjects able to use Ventolin on an 'as required for symptoms' basis
Exclusion criteria:
Subjects who have been hospitalised for their asthma within 4 weeks of visit 1
Subjects who had an acute upper respiratory tract infection within 2 weeks or a lower respiratory tract infection within 4 weeks prior to visit 1
Subjects who received oral, parental or depot corticosteroids within 4 weeks prior to visit 1
Subjects who have a known respiratory disorder other than asthma and/or systemic/thoracic abnormalities which influence normal lung function
Subjects with a disorder that affects growth (e.g. Turner's syndrome)
Subjects who have received any investigational drugs within 4 weeks of visit 1
Subjects with a known or suspected hypersensitivity to inhaled steroids, β2-agonists or lactose
Subjects who use any medication that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole
Subjects who concurrently participate in another clinical study
Subjects who have previously been randomised in this trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Almere
ZIP/Postal Code
1315 RA
Country
Netherlands
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Arnhem
ZIP/Postal Code
6815 AD
Country
Netherlands
Facility Name
GSK Investigational Site
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
GSK Investigational Site
City
Den Haag
ZIP/Postal Code
2566 MJ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Eindhoven
ZIP/Postal Code
5623 EJ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Enschede
ZIP/Postal Code
7511JX
Country
Netherlands
Facility Name
GSK Investigational Site
City
Gouda
ZIP/Postal Code
2803 HG
Country
Netherlands
Facility Name
GSK Investigational Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Helmond
ZIP/Postal Code
5707 HA
Country
Netherlands
Facility Name
GSK Investigational Site
City
Hoorn
ZIP/Postal Code
1624 NP
Country
Netherlands
Facility Name
GSK Investigational Site
City
Leeuwarden
ZIP/Postal Code
8934 AD
Country
Netherlands
Facility Name
GSK Investigational Site
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
GSK Investigational Site
City
Nijmegen
ZIP/Postal Code
6532 SZ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Sittard
ZIP/Postal Code
6131 BK
Country
Netherlands
Facility Name
GSK Investigational Site
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
GSK Investigational Site
City
Veldhoven
ZIP/Postal Code
5504 DB
Country
Netherlands
Facility Name
GSK Investigational Site
City
Zwolle
ZIP/Postal Code
8025 AB
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
20622031
Citation
Vaessen-Verberne AA, van den Berg NJ, van Nierop JC, Brackel HJ, Gerrits GP, Hop WC, Duiverman EJ; COMBO Study Group. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1221-7. doi: 10.1164/rccm.201002-0193OC. Epub 2010 Jul 9.
Results Reference
derived
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Treatment Of Symptomatic Asthma In Children
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