Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy
BACKGROUND: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatmen...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820901/ https://www.ncbi.nlm.nih.gov/pubmed/27044326 http://dx.doi.org/10.1186/s12931-016-0353-4 |
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author | Oliver, Amanda J. Covar, Ronina A. Goldfrad, Caroline H. Klein, Ryan M. Pedersen, Søren E. Sorkness, Christine A. Tomkins, Susan A. Villarán, César Grigg, Jonathan |
author_facet | Oliver, Amanda J. Covar, Ronina A. Goldfrad, Caroline H. Klein, Ryan M. Pedersen, Søren E. Sorkness, Christine A. Tomkins, Susan A. Villarán, César Grigg, Jonathan |
author_sort | Oliver, Amanda J. |
collection | PubMed |
description | BACKGROUND: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose–response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. METHODS: This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5–11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV(1)) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. RESULTS: In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV(1) was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28–33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period. CONCLUSION: VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed. TRIAL REGISTRATION: NCT01573767 (ClinicalTrials.gov). |
format | Online Article Text |
id | pubmed-4820901 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48209012016-04-06 Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy Oliver, Amanda J. Covar, Ronina A. Goldfrad, Caroline H. Klein, Ryan M. Pedersen, Søren E. Sorkness, Christine A. Tomkins, Susan A. Villarán, César Grigg, Jonathan Respir Res Research BACKGROUND: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose–response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. METHODS: This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5–11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV(1)) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. RESULTS: In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV(1) was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28–33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period. CONCLUSION: VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed. TRIAL REGISTRATION: NCT01573767 (ClinicalTrials.gov). BioMed Central 2016-04-05 2016 /pmc/articles/PMC4820901/ /pubmed/27044326 http://dx.doi.org/10.1186/s12931-016-0353-4 Text en © Oliver et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Oliver, Amanda J. Covar, Ronina A. Goldfrad, Caroline H. Klein, Ryan M. Pedersen, Søren E. Sorkness, Christine A. Tomkins, Susan A. Villarán, César Grigg, Jonathan Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
title | Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
title_full | Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
title_fullStr | Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
title_full_unstemmed | Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
title_short | Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
title_sort | randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820901/ https://www.ncbi.nlm.nih.gov/pubmed/27044326 http://dx.doi.org/10.1186/s12931-016-0353-4 |
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