Trial Outcomes & Findings for Nebulized Fluticasone Propionate VS Oral Prednisone in Chinese Pediatric and Adolescent Subjects With an Acute Exacerbation of Asthma (NCT NCT01687296)

NCT ID: NCT01687296

Last Updated: 2018-06-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 261 participants
• Primary outcome timeframe: Days 2 to 8
• Results posted on: 2018-06-20

Participant Flow

The study was planned on 250 Chinese paediatric and adolescent participants (aged 4 to 16 years) with an acute exacerbation of asthma and was conducted at 11 centres in China from 12th November 2012 to 21st June 2013.

A total of 266 participants (par) were screened for this study. Of these, 5 participants were screen failures. A total of 261 participants were randomized to receive either nebulized fluticasone or oral prednisone. A total of 251 participants received at least a single dose study drug.

Participant milestones

Measure	Fluticasone Propionate Participants received fluticasone propionate inhalation solution twice daily (BID) 2x0.5 milligrams (mg)/millilitres (mL) via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone Participants received oral prednisone tablets once daily at 2 mg per kilogram (kg) per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Overall Study STARTED	123	128
Overall Study COMPLETED	116	123
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Measure	Fluticasone Propionate Participants received fluticasone propionate inhalation solution twice daily (BID) 2x0.5 milligrams (mg)/millilitres (mL) via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone Participants received oral prednisone tablets once daily at 2 mg per kilogram (kg) per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Overall Study Lack of Efficacy	1	1
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	6	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Fluticasone Propionate n=123 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Total n=251 Participants Total of all reporting groups
Age, Continuous	6.6 Years STANDARD_DEVIATION 2.41 • n=5 Participants	6.5 Years STANDARD_DEVIATION 2.32 • n=7 Participants	6.5 Years STANDARD_DEVIATION 2.36 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	51 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	77 Participants n=7 Participants	149 Participants n=5 Participants
Region of Enrollment China	123 Participants n=5 Participants	128 Participants n=7 Participants	251 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 2 to 8

Population: ITT Population comprised of all participants randomized to treatment and who received at least one dose of study drug. Data is presented for the participants available at the time of assessment.

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.

Outcome measures

Measure	Fluticasone Propionate n=121 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=124 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Mean Morning Peak Expiratory Flow (AM PEF) on Diary Card Over the Treatment Assessment Period in Intent-to-Treat (ITT) Population	188.77 Litres per minute (L/min) Standard Error 3.774	188.31 Litres per minute (L/min) Standard Error 3.790

PRIMARY outcome

Timeframe: Days 2 to 8

Population: PP Population comprised of all participants in the ITT Population who did not have any full protocol violations which could impact treatment effect. Data is presented for the participants available at the time of assessment.

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.

Outcome measures

Measure	Fluticasone Propionate n=114 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=120 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Mean Morning PEF on Diary Card Over the Treatment Assessment Period in Per Protocol (PP) Population	189.46 L/min Standard Error 3.724	188.96 L/min Standard Error 3.712

SECONDARY outcome

Timeframe: Days 1/2 to 8

Population: ITT Population. Data is presented for the participants available at the time of assessment.

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.

Outcome measures

Measure	Fluticasone Propionate n=121 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=123 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Mean Evening PEF on Diary Card Over the Treatment Assessment Period	195.79 L/min Standard Error 3.723	194.63 L/min Standard Error 3.751

SECONDARY outcome

Timeframe: Days 2 to 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Fluticasone Propionate n=123 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Median Day-time and Night-time Symptom Scores Over the Treatment Assessment Period Day-time symptom score	0.5 Scores on a scale Interval 0.0 to 3.0	1.0 Scores on a scale Interval 0.0 to 3.0
Median Day-time and Night-time Symptom Scores Over the Treatment Assessment Period Night-time symptom score	0.0 Scores on a scale Interval 0.0 to 3.0	0.0 Scores on a scale Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: Days 2 to 8

Population: ITT Population. Data is presented for the participants available at the time of assessment.

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.

Outcome measures

Measure	Fluticasone Propionate n=121 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=123 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Median Number of Use of Rescue Medications During Day and Night Over the Treatment Assessment Period	2.0 Number of use of rescue medication Interval 0.0 to 3.0	2.0 Number of use of rescue medication Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: During the treatment period at Day 5, Day 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Fluticasone Propionate n=123 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period FEV1, Day 8	1.400 Litres Standard Error 0.0294	1.396 Litres Standard Error 0.0280
Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period FVC, Day 5	1.476 Litres Standard Error 0.0454	1.543 Litres Standard Error 0.0439
Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period FVC, Day 8	1.544 Litres Standard Error 0.0326	1.582 Litres Standard Error 0.0316
Clinical Assessment of Lung Function of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) During the Treatment Period FEV1, Day 5	1.288 Litres Standard Error 0.0348	1.331 Litres Standard Error 0.0332

SECONDARY outcome

Timeframe: Baseline, Day 5 and Day 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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

Outcome measures

Measure	Fluticasone Propionate n=123 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Mean Change From Baseline in Clinical Scoring Index at Day 5 and Day 8 Day 8	-3.4 Scores on a scale Standard Deviation 1.26	-3.4 Scores on a scale Standard Deviation 1.26
Mean Change From Baseline in Clinical Scoring Index at Day 5 and Day 8 Day 5	-2.7 Scores on a scale Standard Deviation 1.41	-2.6 Scores on a scale Standard Deviation 1.44

SECONDARY outcome

Timeframe: Day 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Fluticasone Propionate n=123 Participants Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 Participants Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Mean Global Evaluation for Efficacy by Participant/Parent and Investigator Investigator global evaluation	1.5 Scores on a scale Standard Deviation 0.56	1.5 Scores on a scale Standard Deviation 0.52
Mean Global Evaluation for Efficacy by Participant/Parent and Investigator Participant/parent global evaluation	1.5 Scores on a scale Standard Deviation 0.59	1.5 Scores on a scale Standard Deviation 0.52

Adverse Events

Fluticasone Propionate

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Prednisone

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fluticasone Propionate n=123 participants at risk Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 participants at risk Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Infections and infestations Upper respiratory tract infection	0.81% 1/123 • On- treatment serious adverse events (SAE) and non- serious adverse events (AE) were collected from start of study medication through the treatment phase up to 8 days (only on-treatment events captured). Safety Population comprised of participants randomized to treatment and who receive d at least one dose of study drug. Participants were assigned to the treatment group as per treatment actually received.	1.6% 2/128 • On- treatment serious adverse events (SAE) and non- serious adverse events (AE) were collected from start of study medication through the treatment phase up to 8 days (only on-treatment events captured). Safety Population comprised of participants randomized to treatment and who receive d at least one dose of study drug. Participants were assigned to the treatment group as per treatment actually received.

Other adverse events

Measure	Fluticasone Propionate n=123 participants at risk Participants received fluticasone propionate inhalation solution BID 2x0.5 mg/mL via a nebulizer in morning and evening for 7 days. Blinding was maintained by administration of placebo soluble tablets once daily in the morning for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.	Prednisone n=128 participants at risk Participants received oral prednisone tablets once daily at 2 mg per kg per day, up to 40 mg per day for 4 days, then 1 mg per kg per day or half of the original dose, up to 20 mg per day for 3 days in the morning. Blinding was maintained by administration of placebo nebules 2×2mL 0.9% saline BID in morning and evening for 7 days. Salbutamol was provided on a needed basis throughout the treatment period.
Investigations White blood cell count increased	0.81% 1/123 • On- treatment serious adverse events (SAE) and non- serious adverse events (AE) were collected from start of study medication through the treatment phase up to 8 days (only on-treatment events captured). Safety Population comprised of participants randomized to treatment and who receive d at least one dose of study drug. Participants were assigned to the treatment group as per treatment actually received.	7.8% 10/128 • On- treatment serious adverse events (SAE) and non- serious adverse events (AE) were collected from start of study medication through the treatment phase up to 8 days (only on-treatment events captured). Safety Population comprised of participants randomized to treatment and who receive d at least one dose of study drug. Participants were assigned to the treatment group as per treatment actually received.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER