Nebulized Fluticasone Propionate VS Oral Prednisone in Chinese Pediatric and Adolescent Subjects With an Acute Exacerbation of Asthma

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01687296
• Other study ID #: 114220
• Status: Completed
• Phase: Phase 3
• Start date: November 12, 2012
• Est. completion date: June 21, 2013

Study information

• Verified date: June 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: June 21, 2013
• Est. primary completion date: June 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 16 Years

Eligibility

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 ß2 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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• fluticasone propionate inhalation solution
2×0.5mg/2ml twice daily nebulized to treat an acute exacerbation of asthma for 7 days
• oral prednisone
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
• placebo inhalation solution
4ml 0.9% saline nebulized twice daily
• placebo tablet
placebo soluble tablet, oral ,once daily
• salbutamol
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.

Locations

Country	Name	City	State
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Wenzhou	Zhejiang
China	GSK Investigational Site	Wuxi
China	GSK Investigational Site	Yanji	Jilin

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Days 2 to 8
Primary	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.	Days 2 to 8
Secondary	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.	Days 1/2 to 8
Secondary	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.	Days 2 to 8
Secondary	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.	Days 2 to 8
Secondary	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.	During the treatment period at Day 5, Day 8
Secondary	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	Baseline, Day 5 and Day 8
Secondary	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.	Day 8