Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre–school-age children with asthma: A randomized, double-blind, placebo-controlled study

doi:10.1016/j.jpeds.2006.07.045

The Journal of Pediatrics

Volume 149, Issue 5, November 2006, Pages 663-670.e1

Originally presented in abstract form at the Annual Meeting of the American Academy of Allergy Asthma and Immunology, March 18-22, 2005, San Antonio, TX and published in J Allergy Clin Immunol 2005;115(Suppl 1):S4-5; abstract S211.

https://doi.org/10.1016/j.jpeds.2006.07.045 Get rights and content

Objective

To evaluate the efficacy and tolerability of fluticasone propionate (FP) hydrofluoroalkane (HFA) in children age 1 to < 4 years with asthma.

Study design

Children were assigned (2:1) to receive FP HFA 88 μg (n = 239) or placebo HFA (n = 120) twice daily through a metered-dose inhaler with a valved holding chamber and attached facemask for 12 weeks. The primary efficacy measure was mean percent change from baseline to endpoint in 24-hour daily (composite of daytime and nighttime) asthma symptom scores.

Results

The FP-treated children had significantly greater (P ≤ .05) reductions in 24-hour daily asthma symptom scores (−53.9% vs −44.1%) and nighttime symptom scores over the entire treatment period compared with the placebo group. Daytime asthma symptom scores and albuterol use were slightly more decreased with FP than with placebo; however, the differences were not statistically significant. Increases in the percentage of symptom-free days were comparable. The percentage of patients who experienced at least 1 adverse event was similar in the 2 groups. Baseline median urinary cortisol excretion values were comparable between the groups, and there was little change from baseline at endpoint. FP plasma concentrations demonstrated that systemic exposure was low.

Conclusions

FP HFA 88 μg twice daily was effective and well tolerated in pre–school-age children with asthma.

Section snippets

Patients

This study evaluated children age 1 to < 4 years with a history of symptomatic asthma who had experienced 2 or more episodes of increased asthma symptoms requiring medical attention and asthma treatment within the year before screening. During the 4 weeks before screening, the children must have reported treatment with a short-acting beta-agonist for relief of respiratory symptoms 3 or more times per week.

Exclusion criteria included the following: before screening, low-dose ICS or intranasal

Patients

Of the 572 children screened, 359 (239 in the FP HFA group and 120 in the placebo HFA group) were randomized to treatment. Stratification by age was achieved, with 31% of the placebo HFA group and 30% of the FP HFA group age 1 to < 2 years at randomization. The most common reason for not being randomized was failure to meet the average weekly asthma symptom score (≥ 1.1) criterion. Demographic and baseline clinical characteristics were similar in the 2 treatment groups (Table I). Mean baseline

Discussion

National and international asthma management guidelines recommend that children with mild, moderate, or severe persistent asthma be preferentially treated with a regimen that includes an ICS.11, 12, 13 In children age 1 to < 4 years, FP HFA 88 μg twice daily was significantly more effective than placebo at improving 24-hour daily and nighttime asthma symptom scores.

At endpoint, the mean percent reduction in 24-hour daily asthma symptom scores was approximately 10% greater in the FP HFA group

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However, as the MCh challenge was only performed at a subgroup of sites, the study may not have been sufficiently powered for this variable. A placebo arm might have facilitated the interpretation of this result; however, this was not included because low doses of both ciclesonide and fluticasone propionate have previously been demonstrated to be clinically more effective than placebo in controlling asthma and improving lung function in patients with persistent asthma [8,26,27]. Furthermore, 12 weeks of treatment with placebo in patients with moderate and severe asthma would have been deemed unacceptable by many ethics committees and could have caused excessive dropouts.
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FEV₁ and morning PEF increased from baseline in all groups (p < 0.0001). Ciclesonide 160 μg was not inferior to fluticasone propionate 176 μg for FEV₁ (p = 0.0030, one-sided). In all groups, asthma symptom score sums and rescue medication use significantly improved (p < 0.0001). The percentages of asthma symptom-, rescue medication- and nocturnal awakening-free days were high, with no significant differences between treatments. Quality of life scores improved with all treatments (p < 0.0001). A significant dose–response occurred between low and higher doses of ciclesonide for exacerbations and asthma control definitions. The incidences of adverse events were comparable across treatments. Urine free cortisol levels decreased significantly with fluticasone propionate (p = 0.0103), but not with ciclesonide.
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In a double-blind, randomized, placebo-controlled study in 332 asthmatic children aged 24–47 months, fluticasone propionate 44 or 88 μg bd for 12 weeks had no effect on growth velocity or 12-hour overnight urinary cortisol excretion (16C). There were similar results in 359 asthmatic children aged 1–4 years randomized to fluticasone propionate 88 μg bd or placebo for 12 weeks (23C). In 24 asthmatic children randomized to beclomethasone dipropionate 100 μg bd or budesonide 100 or 200 μg bd in a double-blind crossover study, lower leg growth rate over 3 months did not differ between the groups (24c).
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: Supported by a grant from GlaxoSmithKline. Drs. Qaqundah, Sugerman, Ceruti, and Maspero are Investigators for GlaxoSmithKline; Mr. Kleha, Ms. Scott, and Drs. Wu, Mehta, and Crim are employees of GlaxoSmithKline.

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Original articleEfficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre–school-age children with asthma: A randomized, double-blind, placebo-controlled study

Objective

Study design

Results

Conclusions

Section snippets

Patients

Patients

Discussion

Ann Asthma Allergy Imunol

Respir Med

Respir Med

Respir Med

Ann Asthma Allergy Immunol

Respir Med

J Allergy Clin Immunol

Clin Ther

J Allergy Clin Immunol

Inflammation in childhood asthma and other wheezing disorders

Pediatrics

Flovent® (fluticasone propionate) inhalation aerosol prescribing information [package insert]

Fluticasone propionate 100 μg bid using a non-CFC propellant, HFA 134a, in asthmatic children

Can Respir J

The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study

Am J Respir Crit Care Med

Original article
Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre–school-age children with asthma: A randomized, double-blind, placebo-controlled study