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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
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
_version_ 1782425490822266880
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
work_keys_str_mv AT oliveramandaj randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT covarroninaa randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT goldfradcarolineh randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT kleinryanm randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT pedersensørene randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT sorknesschristinea randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT tomkinssusana randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT villarancesar randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy
AT griggjonathan randomisedtrialofoncedailyvilanterolinchildrenwithasthmaoninhaledcorticosteroidtherapy