Back to resultsNebulized Fluticasone Propionate VS Oral Prednisone in Chinese Pediatric and Adolescent Subjects With an Acute Exacerbation of Asthma
Primary Purpose
Asthma
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
fluticasone propionate inhalation solution
oral prednisone
placebo inhalation solution
placebo tablet
salbutamol
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring PEF, inhaled, Fluticasone Propionate, safety, prednisone, acute exacerbation, asthma, efficacy
Eligibility Criteria
Inclusion Criteria:
- Chinese male and female pediatric or adolescent subjects aged 4 to 16 years, inclusive
- Subjects have an established diagnosis of asthma
- The definition of asthma. According to Chinese Guideline for the diagnosis and optimal management of asthma in children [Respiratory branch of pediatric society,Chinese Medical. Association. 2008, revised version], the subjects can be diagnosed when meeting the criteria. The diagnosis criteria is listed in the protocol.
- The severity of an acute exacerbation of asthma is defined as PEF of 50% to 75% predicted via a peak flow meter, with a clinical scoring index of ≥2. The clinical scoring index represents the sum of the score for each of four signs: respiratory rate (0=low to 3=high, dependent on age), wheezing (0=none to 3=severe), inspiration/expiration ratio (0=2:1 to 3=1:3), and accessory muscle (0=none to 3=marked use).
- Subjects can properly use a mini-wright peak flow meter, nebulizer and MDI with/without a spacer, and accurately complete a diary card with parental assistance, if required.
- Subjects' parents/guardians are willing to give written informed consent.
Exclusion criteria:
- Severe respiratory dysfunction.
- History of mechanical ventilation due to respiratory failure.
- Admission to hospital due to respiratory disease within the previous 2 weeks, including asthmatic exacerbations.
- Clinical or lab evidence of a serious, uncontrolled systemic disease or presence of any disease likely to interfere with the objectives of this study, such as pulmonary cystic fibrosis and bronchopulmonary dysplasia.
- Known or suspected hypersensitivity to glucocorticosteroids or β2 agonists.
- Clinical visual evidence of oral candidiasis at Visit1.
- Use of the medications below in Table 1 according to the following defined time intervals prior to presentation. The list is provided in the protocol.
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
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
fluticasone Nebules/placebo tablet
oral prednisone/placebo inhalation solution
Arm Description
2×0.5mg/2ml twice daily neblulized/placebo tablet, oral, once daily
once daily (2mg/kg.day, up to 40mg/day for 4 days, then 1mg/kg.day or half of the original dose, up to 20mg/day for 3 days) / placebo inhalation solution nebulized twice daily
Outcomes
Primary Outcome Measures
Mean Morning Peak Expiratory Flow (AM PEF) on Diary Card Over the Treatment Assessment Period in Intent-to-Treat (ITT) Population
PEF is the maximum flow generated during a forceful exhalation, starting from full lung inflation. Participants (if needed with the help of parents or guardian) recorded on diary card the best of three PEF measurements, using a mini-Wright peak flow meter in the morning before taking any study drug. Only data that was drawn from Days 2 to 8 after randomization and on or before one day after the end date of study drug was used for analysis. The outcome measure was considered missing if less than 2 days were recorded in the given treatment assessment period. Two participants from fluticasone propionate group and 4 participants from prednisone group had the missing outcome measure. Analysis was performed using an analysis of covariance (ANCOVA) model with effects due to gender, age, centre and treatment group.
Mean Morning PEF on Diary Card Over the Treatment Assessment Period in Per Protocol (PP) Population
PEF is the maximum flow generated during a forceful exhalation, starting from full lung inflation. Participants (if needed with the help of parents or guardian) recorded on diary card the best of three PEF measurements, using a mini-Wright peak flow meter in the morning before talking any study drug. Only data that was drawn from Days 2 to 8 after randomization and on or before one day after the end date of study drug was used for analysis. The outcome measure was considered missing if less than 2 days were recorded in the given treatment assessment period. Two participants from fluticasone propionate group and 5 participants from prednisone group had the missing outcome measure. Analysis was performed using ANCOVA model with effects due to gender, age ,centre and treatment group.
Secondary Outcome Measures
Mean Evening PEF on Diary Card Over the Treatment Assessment Period
PEF is the maximum flow generated during a forceful exhalation, starting from full lung inflation. Participants recorded on diary card the best of three PEF measurements, using a mini-Wright peak flow meter in the evening (6:00-9:00 post meridiem [PM]) before taking any study drug. Only data that was drawn from Days 1/2 to 8 after randomization and before or on the end date of study drug was used for analysis. If participants started to take the study drug in the morning (early or on 12:00 PM), only then the evening PEF on the date of randomization was used. The outcome measure was considered missing if less than 2 days was recorded in the given treatment assessment period. Two participants from fluticasone propionate group and 5 participants from prednisone group had the missing outcome measure. Analysis was performed using an ANCOVA model with effects due to gender, age, centre and treatment group.
Median Day-time and Night-time Symptom Scores Over the Treatment Assessment Period
The symptoms of cough, sputum production, wheeze and dyspnoea were assessed in morning and evening, and recorded on participant diary cards. Day-time symptoms were scored while retiring to bed on a scale of 0 (no symptoms) to 5 (severe). Night-time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). For day-time score, only data that was from Days 2 to 8 after randomization and before or on the end date of study drug was used. For night-time score, only data that are from Days 2 to 8 after randomization and on or before one day after the end date of study drug was used. The outcome measure was considered missing if less than 2 days were recorded in the given treatment assessment period. The analysis only includes participants with at least 2 days of non-missing symptom scores in the given treatment assessment period.
Median Number of Use of Rescue Medications During Day and Night Over the Treatment Assessment Period
The use of nebulized salbutamol (doses/puffs and frequency) were recorded on diary card in the morning and evening. The median numbers of times of use of rescue medication during day and night was calculated for each participant over the treatment assessment period. In each case, only data that was from Days 2 to 8 after randomization and before or on the end date of study drug was used. The outcome measure was considered missing if less than 2 days (that is., 24-hour periods) were recorded in the given treatment assessment period. The analysis only includes participants who have at least 2 days of non-missing numbers of times rescue medication (including zero) in the given treatment assessment period.
Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period
Spirometric assessments of FEV1 and FVC were assessed at clinic visit 1 (Screening), 2 (Day 5) and 3 (Day 8). Lung function tests were performed at the approximately same time at each visit in the morning. Participants were instructed to withhold salbutamol therapy for at least 4 hour, and the highest of three FEV1 and FVC measurements were recorded. If participants discontinued before or on Day 5, then the FEV1 and FVC collected at the early withdrawal visit is included in the Visit 2. Otherwise, the FEV1, FVC collected at the early withdrawal visit was included in the Visit 3. Analysis was performed using ANCOVA with covariates of gender, centre, age and treatment.
Mean Change From Baseline in Clinical Scoring Index at Day 5 and Day 8
The clinical scoring index was assessed at Baseline (Visit 1), Day 5 and Day 8. The score assigned represented the sum of the score for each of four signs: respiratory rate, wheezing, inspiration/expiration ratio, and accessory muscle use. Each of these parameters were scored on a 4-point scale of 0 to 3 where 0=none, 1=mild, 2=moderate and 3=severe. The total score ranged from 0 to 12, where 0 indicated absence of symptoms and 12 indicated most severe symptoms. The Baseline value was the last non-missing value prior to randomization. Change from Baseline was calculated/defined as value at the indicated visit minus value at the Baseline. A negative value of change in score from Baseline indicated improvement in severity of symptoms. If participants discontinued before or on Day 5, then the clinical scoring index collected at the early withdrawal visit was included in the Visit 2. Otherwise, the clinical scoring index collected at the early withdrawal visit was included in the Visit 3
Mean Global Evaluation for Efficacy by Participant/Parent and Investigator
At Visit 3 (Day 8), participant/parent and investigator were asked to evaluate efficacy globally as very beneficial=1, beneficial=2, no effect=3 or worse=4. The global evaluation collected at the early withdrawal visit was included in the Visit 3. If participants were discontinued at Visit 2, then the global evaluation collected at the Visit 2 is also included in the Visit 3 for summary and analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01687296
Brief Title
Nebulized Fluticasone Propionate VS Oral Prednisone in Chinese Pediatric and Adolescent Subjects With an Acute Exacerbation of Asthma
Official Title
A Multicentre, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel-group Study to Determine the Efficacy and Safety of Nebulized Fluticasone Propionate 1mg Twice Daily Compared With Oral Prednisone Administered for 7 Days to Chinese Pediatric and Adolescent Subjects (Aged 4 to 16 Years) With an Acute Exacerbation of Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
November 12, 2012 (undefined)
Primary Completion Date
June 1, 2013 (Actual)
Study Completion Date
June 21, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study to determine the efficacy and safety of nebulized fluticasone propionate 1mg twice daily compared with oral prednisone administered for 7 days to Chinese pediatric and adolescent subjects (aged 4 to 16 years) with an acute exacerbation of asthma
Detailed Description
This is a multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study to determine the efficacy and safety of nebulized fluticasone propionate (FP) 1mg twice daily compared with oral prednisone administered for 7 days to Chinese pediatric and adolescent subjects (aged 4 to 16 years) with an acute exacerbation of asthma. This study is for supporting registration of FP Nebules treating Chinese pediatric and adolescent subjects (aged 4 to 16 years) with an acute exacerbation of asthma in China.
At least 250 subjects, aged 4-16 years old, diagnosed an acute exacerbation of asthma at presentation, are eligible to take part in the study if they meet the inclusion criteria. They are randomly assigned at the ratio 1:1 to one of the following treatment groups for 7 days: FP Nebules 2×0.5mg/2ml twice daily/Placebo tablets once daily; Or, Oral prednisone tablets once daily (2mg/kg.day, up to 40mg/day for 4 days, then 1mg/kg.day or half of the original dose, up to 20mg/day for 3 days) / Placebo Nebules 2×2ml 0.9% saline twice daily. While all subjects are given Salbutamol Nebules / MDI for relief of symptoms. After randomization (visit 1), the following visits are on Day5 (visit 2) and Day8 (visit 3), and a follow-up phone call (visit4) will happen two weeks post treatment on Day 21 for collection of adverse events.
The primary endpoint is mean morning PEF on diary card over the treatment assessment period. The secondary endpoints include subject derived data (symptom scores ), evening PEF on diary card, use of rescue medications, clinic assessments of pulmonary function ( FEV1, and FVC) , clinical scoring index , patient/parent and investigator global evaluation, and use of rescue medications during the trial. Safety endpoints include AEs, vital signs, and oropharyngeal examinations, and laboratory tests (haematology, urinalysis, chemistry). The subjects are assessed for compliance on completion of diary card.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
PEF, inhaled, Fluticasone Propionate, safety, prednisone, acute exacerbation, asthma, efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
261 (Actual)
8. Arms, Groups, and Interventions
Arm Title
fluticasone Nebules/placebo tablet
Arm Type
Experimental
Arm Description
2×0.5mg/2ml twice daily neblulized/placebo tablet, oral, once daily
Arm Title
oral prednisone/placebo inhalation solution
Arm Type
Active Comparator
Arm Description
once daily (2mg/kg.day, up to 40mg/day for 4 days, then 1mg/kg.day or half of the original dose, up to 20mg/day for 3 days) / placebo inhalation solution nebulized twice daily
Intervention Type
Drug
Intervention Name(s)
fluticasone propionate inhalation solution
Intervention Description
2×0.5mg/2ml twice daily nebulized to treat an acute exacerbation of asthma for 7 days
Intervention Type
Drug
Intervention Name(s)
oral prednisone
Intervention Description
once daily (2mg/kg.day, up to 40mg/day for 4 days, then 1mg/kg.day or half of the original dose, up to 20mg/day for 3 days) to treat an acute exacerbation of asthma for 7 days
Intervention Type
Drug
Intervention Name(s)
placebo inhalation solution
Intervention Description
4ml 0.9% saline nebulized twice daily
Intervention Type
Drug
Intervention Name(s)
placebo tablet
Intervention Description
placebo soluble tablet, oral ,once daily
Intervention Type
Drug
Intervention Name(s)
salbutamol
Intervention Description
Salbutamol MDI 2 puffs twice daily or Nebules twice daily, and can be increased up to every 4 hours on an as-needed basis, through the treatment period.
Primary Outcome Measure Information:
Title
Mean Morning Peak Expiratory Flow (AM PEF) on Diary Card Over the Treatment Assessment Period in Intent-to-Treat (ITT) Population
Description
PEF is the maximum flow generated during a forceful exhalation, starting from full lung inflation. Participants (if needed with the help of parents or guardian) recorded on diary card the best of three PEF measurements, using a mini-Wright peak flow meter in the morning before taking any study drug. Only data that was drawn from Days 2 to 8 after randomization and on or before one day after the end date of study drug was used for analysis. The outcome measure was considered missing if less than 2 days were recorded in the given treatment assessment period. Two participants from fluticasone propionate group and 4 participants from prednisone group had the missing outcome measure. Analysis was performed using an analysis of covariance (ANCOVA) model with effects due to gender, age, centre and treatment group.
Time Frame
Days 2 to 8
Title
Mean Morning PEF on Diary Card Over the Treatment Assessment Period in Per Protocol (PP) Population
Description
PEF is the maximum flow generated during a forceful exhalation, starting from full lung inflation. Participants (if needed with the help of parents or guardian) recorded on diary card the best of three PEF measurements, using a mini-Wright peak flow meter in the morning before talking any study drug. Only data that was drawn from Days 2 to 8 after randomization and on or before one day after the end date of study drug was used for analysis. The outcome measure was considered missing if less than 2 days were recorded in the given treatment assessment period. Two participants from fluticasone propionate group and 5 participants from prednisone group had the missing outcome measure. Analysis was performed using ANCOVA model with effects due to gender, age ,centre and treatment group.
Time Frame
Days 2 to 8
Secondary Outcome Measure Information:
Title
Mean Evening PEF on Diary Card Over the Treatment Assessment Period
Description
PEF is the maximum flow generated during a forceful exhalation, starting from full lung inflation. Participants recorded on diary card the best of three PEF measurements, using a mini-Wright peak flow meter in the evening (6:00-9:00 post meridiem [PM]) before taking any study drug. Only data that was drawn from Days 1/2 to 8 after randomization and before or on the end date of study drug was used for analysis. If participants started to take the study drug in the morning (early or on 12:00 PM), only then the evening PEF on the date of randomization was used. The outcome measure was considered missing if less than 2 days was recorded in the given treatment assessment period. Two participants from fluticasone propionate group and 5 participants from prednisone group had the missing outcome measure. Analysis was performed using an ANCOVA model with effects due to gender, age, centre and treatment group.
Time Frame
Days 1/2 to 8
Title
Median Day-time and Night-time Symptom Scores Over the Treatment Assessment Period
Description
The symptoms of cough, sputum production, wheeze and dyspnoea were assessed in morning and evening, and recorded on participant diary cards. Day-time symptoms were scored while retiring to bed on a scale of 0 (no symptoms) to 5 (severe). Night-time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). For day-time score, only data that was from Days 2 to 8 after randomization and before or on the end date of study drug was used. For night-time score, only data that are from Days 2 to 8 after randomization and on or before one day after the end date of study drug was used. The outcome measure was considered missing if less than 2 days were recorded in the given treatment assessment period. The analysis only includes participants with at least 2 days of non-missing symptom scores in the given treatment assessment period.
Time Frame
Days 2 to 8
Title
Median Number of Use of Rescue Medications During Day and Night Over the Treatment Assessment Period
Description
The use of nebulized salbutamol (doses/puffs and frequency) were recorded on diary card in the morning and evening. The median numbers of times of use of rescue medication during day and night was calculated for each participant over the treatment assessment period. In each case, only data that was from Days 2 to 8 after randomization and before or on the end date of study drug was used. The outcome measure was considered missing if less than 2 days (that is., 24-hour periods) were recorded in the given treatment assessment period. The analysis only includes participants who have at least 2 days of non-missing numbers of times rescue medication (including zero) in the given treatment assessment period.
Time Frame
Days 2 to 8
Title
Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period
Description
Spirometric assessments of FEV1 and FVC were assessed at clinic visit 1 (Screening), 2 (Day 5) and 3 (Day 8). Lung function tests were performed at the approximately same time at each visit in the morning. Participants were instructed to withhold salbutamol therapy for at least 4 hour, and the highest of three FEV1 and FVC measurements were recorded. If participants discontinued before or on Day 5, then the FEV1 and FVC collected at the early withdrawal visit is included in the Visit 2. Otherwise, the FEV1, FVC collected at the early withdrawal visit was included in the Visit 3. Analysis was performed using ANCOVA with covariates of gender, centre, age and treatment.
Time Frame
During the treatment period at Day 5, Day 8
Title
Mean Change From Baseline in Clinical Scoring Index at Day 5 and Day 8
Description
The clinical scoring index was assessed at Baseline (Visit 1), Day 5 and Day 8. The score assigned represented the sum of the score for each of four signs: respiratory rate, wheezing, inspiration/expiration ratio, and accessory muscle use. Each of these parameters were scored on a 4-point scale of 0 to 3 where 0=none, 1=mild, 2=moderate and 3=severe. The total score ranged from 0 to 12, where 0 indicated absence of symptoms and 12 indicated most severe symptoms. The Baseline value was the last non-missing value prior to randomization. Change from Baseline was calculated/defined as value at the indicated visit minus value at the Baseline. A negative value of change in score from Baseline indicated improvement in severity of symptoms. If participants discontinued before or on Day 5, then the clinical scoring index collected at the early withdrawal visit was included in the Visit 2. Otherwise, the clinical scoring index collected at the early withdrawal visit was included in the Visit 3
Time Frame
Baseline, Day 5 and Day 8
Title
Mean Global Evaluation for Efficacy by Participant/Parent and Investigator
Description
At Visit 3 (Day 8), participant/parent and investigator were asked to evaluate efficacy globally as very beneficial=1, beneficial=2, no effect=3 or worse=4. The global evaluation collected at the early withdrawal visit was included in the Visit 3. If participants were discontinued at Visit 2, then the global evaluation collected at the Visit 2 is also included in the Visit 3 for summary and analysis.
Time Frame
Day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chinese male and female pediatric or adolescent subjects aged 4 to 16 years, inclusive
Subjects have an established diagnosis of asthma
The definition of asthma. According to Chinese Guideline for the diagnosis and optimal management of asthma in children [Respiratory branch of pediatric society,Chinese Medical. Association. 2008, revised version], the subjects can be diagnosed when meeting the criteria. The diagnosis criteria is listed in the protocol.
The severity of an acute exacerbation of asthma is defined as PEF of 50% to 75% predicted via a peak flow meter, with a clinical scoring index of ≥2. The clinical scoring index represents the sum of the score for each of four signs: respiratory rate (0=low to 3=high, dependent on age), wheezing (0=none to 3=severe), inspiration/expiration ratio (0=2:1 to 3=1:3), and accessory muscle (0=none to 3=marked use).
Subjects can properly use a mini-wright peak flow meter, nebulizer and MDI with/without a spacer, and accurately complete a diary card with parental assistance, if required.
Subjects' parents/guardians are willing to give written informed consent.
Exclusion criteria:
Severe respiratory dysfunction.
History of mechanical ventilation due to respiratory failure.
Admission to hospital due to respiratory disease within the previous 2 weeks, including asthmatic exacerbations.
Clinical or lab evidence of a serious, uncontrolled systemic disease or presence of any disease likely to interfere with the objectives of this study, such as pulmonary cystic fibrosis and bronchopulmonary dysplasia.
Known or suspected hypersensitivity to glucocorticosteroids or β2 agonists.
Clinical visual evidence of oral candidiasis at Visit1.
Use of the medications below in Table 1 according to the following defined time intervals prior to presentation. The list is provided in the protocol.
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
Changsha
State/Province
Hunan
ZIP/Postal Code
410005
Country
China
Facility Name
GSK Investigational Site
City
Yanji
State/Province
Jilin
ZIP/Postal Code
133000
Country
China
Facility Name
GSK Investigational Site
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110004
Country
China
Facility Name
GSK Investigational Site
City
Wenzhou
State/Province
Zhejiang
ZIP/Postal Code
323027
Country
China
Facility Name
GSK Investigational Site
City
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
GSK Investigational Site
City
Beijing
Country
China
Facility Name
GSK Investigational Site
City
Changchun
Country
China
Facility Name
GSK Investigational Site
City
Chongqing
ZIP/Postal Code
400014
Country
China
Facility Name
GSK Investigational Site
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
GSK Investigational Site
City
Shanghai
ZIP/Postal Code
200092
Country
China
Facility Name
GSK Investigational Site
City
Wuxi
ZIP/Postal Code
214023
Country
China
12. IPD Sharing Statement
Learn more about this trial
Nebulized Fluticasone Propionate VS Oral Prednisone in Chinese Pediatric and Adolescent Subjects With an Acute Exacerbation of Asthma
We'll reach out to this number within 24 hrs