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
Overview
- Phase
- Phase 3
- Intervention
- fluticasone propionate inhalation solution
- Conditions
- Asthma
- Sponsor
- GlaxoSmithKline
- Enrollment
- 261
- Locations
- 1
- Primary Endpoint
- Mean Morning Peak Expiratory Flow (AM PEF) on Diary Card Over the Treatment Assessment Period in Intent-to-Treat (ITT) Population
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
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 ≥
- •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.
Exclusion Criteria
- Not provided
Arms & Interventions
fluticasone Nebules/placebo tablet
2×0.5mg/2ml twice daily neblulized/placebo tablet, oral, once daily
Intervention: fluticasone propionate inhalation solution
fluticasone Nebules/placebo tablet
2×0.5mg/2ml twice daily neblulized/placebo tablet, oral, once daily
Intervention: placebo tablet
fluticasone Nebules/placebo tablet
2×0.5mg/2ml twice daily neblulized/placebo tablet, oral, once daily
Intervention: salbutamol
oral prednisone/placebo inhalation solution
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: oral prednisone
oral prednisone/placebo inhalation solution
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: placebo inhalation solution
oral prednisone/placebo inhalation solution
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: salbutamol
Outcomes
Primary Outcomes
Mean Morning Peak Expiratory Flow (AM PEF) on Diary Card Over the Treatment Assessment Period in Intent-to-Treat (ITT) Population
Time Frame: Days 2 to 8
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
Time Frame: Days 2 to 8
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 Outcomes
- Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period(During the treatment period at Day 5, Day 8)
- Mean Evening PEF on Diary Card Over the Treatment Assessment Period(Days 1/2 to 8)
- Mean Change From Baseline in Clinical Scoring Index at Day 5 and Day 8(Baseline, Day 5 and Day 8)
- Mean Global Evaluation for Efficacy by Participant/Parent and Investigator(Day 8)
- Median Day-time and Night-time Symptom Scores Over the Treatment Assessment Period(Days 2 to 8)
- Median Number of Use of Rescue Medications During Day and Night Over the Treatment Assessment Period(Days 2 to 8)