The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given 'as needed' in mild asthma: study protocols for two randomised controlled trials
Author(s)
Type
Journal Article
Abstract
Background: In many patients with mild asthma, the low frequency of symptoms and the episodic nature of
exacerbations make adherence to regular maintenance treatment difficult. This often leads to over-reliance on
short-acting β2-agonist (SABA) reliever medication and under-treatment of the underlying inflammation, with poor
control of asthma symptoms and increased risk of exacerbations. The use of budesonide/formoterol ‘as needed’ in
response to symptoms may represent an alternative treatment option for patients with mild asthma.
Methods/design: The SYmbicort Given as needed in Mild Asthma (SYGMA) programme consists of two 52-week,
double-blind, randomised, multicentre, parallel-group, phase 3 trials of patients aged 12 years and older with a
clinical diagnosis of asthma for at least 6 months, who would qualify for treatment with regular inhaled
corticosteroids (ICS). SYGMA1 aims to recruit 3750 patients who will be randomised to placebo twice daily (bid)
plus as-needed budesonide/formoterol 160/4.5 μg, placebo bid plus as-needed terbutaline 0.4 mg, or budesonide
200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the superiority of as-needed
budesonide/formoterol over as-needed terbutaline for asthma control, as measured by well-controlled asthma
weeks; a secondary objective is to establish the noninferiority of as-needed budesonide/formoterol versus
maintenance budesonide plus as-needed terbutaline using the same outcome measure. SYGMA2 aims to recruit
4114 patients who will be randomised to placebo bid plus as-needed budesonide/formoterol 160/4.5 μg, or
budesonide 200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the
noninferiority of as-needed budesonide/formoterol over budesonide bid plus as-needed terbutaline as measured by
the annualised severe exacerbation rate. In both studies, use of all blinded study inhalers will be recorded
electronically using Turbuhaler® Usage Monitors.Discussion: Given the known risks of mild asthma, and known poor adherence with regular inhaled corticosteroids,
the results of the SYGMA programme will help to determine the efficacy and safety of as-needed budesonide/
formoterol therapy in mild asthma. Patient recruitment is complete, and completion of the phase 3 studies is
planned in 2017.
Trial registration: ClinicalTrials.gov identifiers: NCT02149199 SYGMA1 and NCT02224157 SYGMA2. Registered on 16
May 2014 and 19 August 2014, respectively.
exacerbations make adherence to regular maintenance treatment difficult. This often leads to over-reliance on
short-acting β2-agonist (SABA) reliever medication and under-treatment of the underlying inflammation, with poor
control of asthma symptoms and increased risk of exacerbations. The use of budesonide/formoterol ‘as needed’ in
response to symptoms may represent an alternative treatment option for patients with mild asthma.
Methods/design: The SYmbicort Given as needed in Mild Asthma (SYGMA) programme consists of two 52-week,
double-blind, randomised, multicentre, parallel-group, phase 3 trials of patients aged 12 years and older with a
clinical diagnosis of asthma for at least 6 months, who would qualify for treatment with regular inhaled
corticosteroids (ICS). SYGMA1 aims to recruit 3750 patients who will be randomised to placebo twice daily (bid)
plus as-needed budesonide/formoterol 160/4.5 μg, placebo bid plus as-needed terbutaline 0.4 mg, or budesonide
200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the superiority of as-needed
budesonide/formoterol over as-needed terbutaline for asthma control, as measured by well-controlled asthma
weeks; a secondary objective is to establish the noninferiority of as-needed budesonide/formoterol versus
maintenance budesonide plus as-needed terbutaline using the same outcome measure. SYGMA2 aims to recruit
4114 patients who will be randomised to placebo bid plus as-needed budesonide/formoterol 160/4.5 μg, or
budesonide 200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the
noninferiority of as-needed budesonide/formoterol over budesonide bid plus as-needed terbutaline as measured by
the annualised severe exacerbation rate. In both studies, use of all blinded study inhalers will be recorded
electronically using Turbuhaler® Usage Monitors.Discussion: Given the known risks of mild asthma, and known poor adherence with regular inhaled corticosteroids,
the results of the SYGMA programme will help to determine the efficacy and safety of as-needed budesonide/
formoterol therapy in mild asthma. Patient recruitment is complete, and completion of the phase 3 studies is
planned in 2017.
Trial registration: ClinicalTrials.gov identifiers: NCT02149199 SYGMA1 and NCT02224157 SYGMA2. Registered on 16
May 2014 and 19 August 2014, respectively.
Date Issued
2017-01-10
Date Acceptance
2016-11-28
Citation
Trials, 2017, 18
ISSN
1745-6215
Publisher
BioMed Central
Journal / Book Title
Trials
Volume
18
Copyright Statement
© The Author(s). 2016 Open Access This 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.
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.
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Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
As-needed
Asthma control
Budesonide/formoterol
Exacerbations
Mild asthma
Prn
Rescue inhaler
SYGMA
INHALED CORTICOSTEROIDS
PERSISTENT ASTHMA
CLINICAL-PRACTICE
RELIEVER THERAPY
EXACERBATIONS
BUDESONIDE
FORMOTEROL
COMBINATION
INTERMITTENT
PREVENTION
Publication Status
Published
Article Number
12