Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02066129

Acronym

STICS

Enrollment

254

Registered

2014-02-19

Start date

2014-07-31

Completion date

2017-04-21

Last updated

2018-07-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma, Fluticasone

Brief summary

The objective of this study is to determine whether, in children receiving low-dose inhaled corticosteroids (ICS), quintupling the dose of inhaled corticosteroids at the onset of symptoms previously associated with upper respiratory illnesses and subsequent asthma exacerbations reduces the rate of severe asthma exacerbations treated with oral corticosteroids.

Detailed description

The study design is a double-blind, parallel-group trial, including a total of 250 participants, ages 5-11 years, with a diagnosis of asthma and a history of at least 1 asthma exacerbation treated with oral corticosteroids in the prior year. All participants will be treated for 48 weeks with open-label fluticasone 44 mcg 2 puffs twice daily. During the 48-week treatment period, participants will receive randomized blinded therapy for 7 days each time they enter the yellow zone (at the onset of symptoms previously associated with upper respiratory illnesses and subsequent asthma exacerbations). Yellow zone therapy will be fluticasone 44 or 220 mcg 2 puffs twice daily.

Interventions

DRUGFluticasone 44 mcg

Fluticasone is an inhaled corticosteroid

DRUGFluticasone 220 mcg

Fluticasone is an inhaled corticosteroid

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

5 Years to 11 Years

Healthy volunteers

Inclusion criteria

* Physician-diagnosed asthma * At least 1 exacerbation treated with systemic (oral or injectable) corticosteroids in the past 12 months * Able to perform reproducible spirometry * Current treatment with step 2 controller therapy \[low-dose ICS, leukotriene receptor antagonist (LTRA)\] OR current treatment with step 3 controller therapy \[low-dose ICS + long-acting beta agonist (LABA), low-dose ICS + LTRA, or medium dose ICS\] with a childhood Asthma Control Test (c-ACT) score of \>19, no more than 2 prednisone treated exacerbations in the past 6 months, prebronchodilator Forced Expiratory Volume at 1 second (FEV1) ≥ 80% predicted and willing to step down therapy OR controller naïve and qualifying for step 2 controller therapy \[asthma symptoms or short acting beta agonist (SABA) use \> 2 days per week or night-time awakenings due to asthma \> 2 nights per month\] * Prebronchodilator FEV1 ≥ 60% predicted * Ability and willingness to provide informed assent * For females of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method. * History of clinical varicella or varicella vaccine

Exclusion criteria

* Systemic (oral or injectable) corticosteroids within previous 2-week period * Current or recent (previous 2-weeks) use of medications known to significantly interact with corticosteroid disposition, including but not limited to carbamazepine, erythromycin, phenobarbital, phenytoin, rifampin, and ketoconazole * Presence of chronic or active lung disease other than asthma * Significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study * A history of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids * History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure * More than 5 prednisone treated exacerbations in the past 12 months * More than 1 hospitalizations lasting \>24 hours for asthma in the past 12 months * History of adverse reactions to ICS preparations or any of their ingredients * Receiving hyposensitization therapy other than an established maintenance regimen (On maintenance regimen for ≥ 3 months) * History of premature birth before 35 weeks gestation

Design outcomes

Primary

Measure	Time frame	Description
Asthma Exacerbations	end of 48 week treatment period	The primary outcome is the rate of severe asthma exacerbations treated with oral corticosteroids during the 48 week treatment period.

Secondary

Measure	Time frame	Description
Yellow Zone Asthma Symptoms	end of 48 week treatment period	Study participants completed a daily symptom diary. They scored the following diary elements on a scale from 0-3 (none-severe): Cough, Wheeze, Trouble Breathing, Interference With Activities. A combined score was calculated as the sum of the 4 elements and ranged from 0 to 12. The study intervention was based on yellow-zones as noted in the Study Description. This outcome was based on diary data including 21 days, beginning 7 days prior to the onset of the yellow-zone intervention and ending 14 days after the onset of the intervention. The total symptom burden outcome was defined as the sum of the combined score on each diary day and ranged from 0 to 252 (max combined score of 12 per day multiplied by 21 days). A score of zero would indicate no symptoms over the entire 21 days. A score of 252 would indicate severe cough, wheeze, shortness of breath, and interference with activities on all of the 21 days.
Yellow Zone Albuterol Use	end of 48 week treatment period	Use of albuterol rescue medication during 7-day yellow zone episodes.
Unscheduled Emergency Department (ED) or Urgent Care Visits for Asthma	end of 48 week treatment period	Rate of emergency department (ED) or urgent care visits for asthma during the 48 week treatment period.
Number of Participants Hospitalized for Asthma	end of 48 week treatment period	Number of participants hospitalized for asthma during the 48 week treatment period.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Fluticasone 44 mcg Fluticasone 44 mcg 2 puffs twice daily for 7 days initiated at the onset of yellow zone symptoms. Fluticasone 44 mcg: Fluticasone is an inhaled corticosteroid	127
Fluticasone 220 mcg Fluticasone 220 mcg 2 puffs twice daily for 7 days initiated at the onset of yellow zone symptoms. Fluticasone 220 mcg: Fluticasone is an inhaled corticosteroid	127
Total	254

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lack of Efficacy	8	10
Overall Study	Lost to Follow-up	13	12
Overall Study	Physician Decision	1	1
Overall Study	Withdrawal by Subject	7	10

Baseline characteristics

Characteristic	Fluticasone 44 mcg	Fluticasone 220 mcg	Total
Age, Continuous	7.9 years STANDARD_DEVIATION 1.9	8.1 years STANDARD_DEVIATION 1.8	8.0 years STANDARD_DEVIATION 1.9
At least one allergen specific immunoglobulin E (IgE) tests	88 Participants	99 Participants	187 Participants
Blood eosinophils	367 cells per cubic millimeter STANDARD_DEVIATION 300	327 cells per cubic millimeter STANDARD_DEVIATION 234	346 cells per cubic millimeter STANDARD_DEVIATION 268
Hospitalized in year prior to enrollment	16 Participants	15 Participants	31 Participants
Number of positive allergen specific IgE tests	4.8 count STANDARD_DEVIATION 4.2	5.2 count STANDARD_DEVIATION 4.5	5.0 count STANDARD_DEVIATION 4.4
Post albuterol forced expiratory volume at one second (FEV1) % of predicted	106.8 percent STANDARD_DEVIATION 15.6	107.8 percent STANDARD_DEVIATION 13.9	107.3 percent STANDARD_DEVIATION 14.8
Race/Ethnicity, Customized Black	29 Participants	27 Participants	56 Participants
Race/Ethnicity, Customized Other	34 Participants	24 Participants	58 Participants
Race/Ethnicity, Customized White	64 Participants	76 Participants	140 Participants
Region of Enrollment United States	127 participants	127 participants	254 participants
Sex: Female, Male Female	47 Participants	44 Participants	91 Participants
Sex: Female, Male Male	80 Participants	83 Participants	163 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 127	0 / 127
other Total, other adverse events	115 / 127	111 / 127
serious Total, serious adverse events	1 / 127	4 / 127

Outcome results

Primary

Asthma Exacerbations

The primary outcome is the rate of severe asthma exacerbations treated with oral corticosteroids during the 48 week treatment period.