AsthmaNet Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS)

HLB02162020a

AsthmaNet-STICS

False

Released

True

True

Coded

False

Clinical Trial

Open BioLINCC Study

Pediatric

Drug: Fluticasone 44 mcg

Drug: Fluticasone 220 mcg

2020-02-04

2022-01-21

2020-02-04

2022-01-21

July 2014-April 2017

DLD

Lung

non-HIV

non-COVID

None

None

No

No

No

No

Yes, For Some Specimens

No

Some subjects allow use of their specimens for genetic use

Asthma

To assess the efficacy and safety of increasing the dose of inhaled glucocorticoids by a factor of 5 for 7 days in school-age children with mild-to-moderate persistent asthma at the early signs of loss of asthma control (“yellow zone”).

Asthma exacerbations are common events, particularly in school-age children. Exacerbations are costly and are associated with considerable complications. In addition, asthma exacerbations may lead to progressive loss of lung function and greater asthma severity over time. Day-to-day asthma symptoms are traditionally controlled through conventional therapies, particularly the daily use of inhaled glucocorticoids; however, they have only partial efficacy in preventing exacerbations.

There is limited evidence available to inform clinicians’ selection and implementation of strategies in the “yellow zone” (i.e., when there are signs of early loss of asthma control) to prevent these early symptoms from progressing to a full asthma exacerbation. Quadrupling the dose of inhaled glucocorticoids was identified as a potentially efficacious intervention in adult patients, but data on the safety or efficacy of an intervention that uses more than a doubled dose of inhaled glucocorticoids are limited in children. The objective of this study was to determine whether quintupling the dose of inhaled corticosteroids at the onset of “yellow zone” symptoms reduces the rate of severe asthma exacerbations treated with oral corticosteroids.

A total of 254 participants (aged 5-11) underwent randomization with 127 participants assigned to the low-dose and high-dose group. A total of 192 participants, including 94 participants in the high-dose group and 98 in the low-dose group, completed the final trial visit.

Eligible participants were required to have mild-to-moderate persistent asthma, at least one asthma exacerbation treated with systemic glucocorticoids in the previous year, and a prebronchodilator FEV1 >80% predicted. Participants were excluded if asthma was too severe (>5 exacerbations in the previous year that had been treated with systemic glucocorticoids), a history of life-threatening asthma and/or if they experienced more than two prednisone-treated exacerbations in the past 6 months.

Prior to randomization, participants were entered into a 4-week run-in period with maintenance low-dose inhaled glucocorticoids (fluticasone) at a dose of 44 μg per inhalation, two inhalations twice daily. Participants were treated for 48 weeks and were randomly assigned 1:1 to either continue the same dose or use a quintupled dose (fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control (“yellow zone”).

Yellow-zone episodes were identified by the occurrence of any of the following: the use of two doses (four inhalations) of rescue albuterol in 6 hours, the use of three doses (six inhalations) of rescue albuterol in 24 hours, or one night awakening that was due to asthma that was treated with albuterol. Participants were provided with a written asthma action plan that instructed them not to wait for the yellow-zone alert from the electronic diary before starting the blinded yellow-zone inhaler.

The green-zone low-dose inhaler was discontinued while the blinded yellow-zone inhaler was used. Conversely, if a participant did not experience a yellow zone episode, the low-dose inhaler was continued throughout the trial.

An electronic diary was completed nightly that measured symptoms, medications, and peak expiratory flows. Participants were blinded to the results of the peak expiratory flow meter and there was no electronic link between the inhaler and the electronic diary. Clinical assessments during the course of the trial included: standing height measurements, spirometry, peripheral-blood eosinophil counts, total serum IgE level and the levels of IgE specific to aeroallergens.

The primary outcome was the rate of severe asthma exacerbations treated with oral corticosteroids during the 48 week treatment period. Secondary outcomes included time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes. Additionally, rates of exposure to inhaled glucocorticoids were assessed.

In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth.

Jackson DJ, Bacharier LB, Mauger DT, et al. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations. N Engl J Med. 2018;378(10):891–901. doi:10.1056/NEJMoa1710988

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Plasma

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