Trial Outcomes & Findings for Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (NCT NCT02066129)

NCT ID: NCT02066129

Last Updated: 2018-07-11

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 254 participants
• Primary outcome timeframe: end of 48 week treatment period
• Results posted on: 2018-07-11

Participant Flow

Participant milestones

Measure	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	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
Overall Study STARTED	127	127
Overall Study COMPLETED	98	94
Overall Study NOT COMPLETED	29	33

Reasons for withdrawal

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

Baseline Characteristics

Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations

Baseline characteristics by cohort

Measure	Fluticasone 44 mcg n=127 Participants 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	Fluticasone 220 mcg n=127 Participants 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	Total n=254 Participants Total of all reporting groups
Age, Continuous	7.9 years STANDARD_DEVIATION 1.9 • n=5 Participants	8.1 years STANDARD_DEVIATION 1.8 • n=7 Participants	8.0 years STANDARD_DEVIATION 1.9 • n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	44 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	83 Participants n=7 Participants	163 Participants n=5 Participants
Race/Ethnicity, Customized White	64 Participants n=5 Participants	76 Participants n=7 Participants	140 Participants n=5 Participants
Race/Ethnicity, Customized Black	29 Participants n=5 Participants	27 Participants n=7 Participants	56 Participants n=5 Participants
Race/Ethnicity, Customized Other	34 Participants n=5 Participants	24 Participants n=7 Participants	58 Participants n=5 Participants
Region of Enrollment United States	127 participants n=5 Participants	127 participants n=7 Participants	254 participants n=5 Participants
Blood eosinophils	367 cells per cubic millimeter STANDARD_DEVIATION 300 • n=5 Participants	327 cells per cubic millimeter STANDARD_DEVIATION 234 • n=7 Participants	346 cells per cubic millimeter STANDARD_DEVIATION 268 • n=5 Participants
Number of positive allergen specific IgE tests	4.8 count STANDARD_DEVIATION 4.2 • n=5 Participants	5.2 count STANDARD_DEVIATION 4.5 • n=7 Participants	5.0 count STANDARD_DEVIATION 4.4 • n=5 Participants
Hospitalized in year prior to enrollment	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Post albuterol forced expiratory volume at one second (FEV1) % of predicted	106.8 percent STANDARD_DEVIATION 15.6 • n=5 Participants	107.8 percent STANDARD_DEVIATION 13.9 • n=7 Participants	107.3 percent STANDARD_DEVIATION 14.8 • n=5 Participants
At least one allergen specific immunoglobulin E (IgE) tests	88 Participants n=5 Participants	99 Participants n=7 Participants	187 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Fluticasone 44 mcg n=127 Participants 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	Fluticasone 220 mcg n=127 Participants 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
Asthma Exacerbations	0.37 exacerbations per year Interval 0.25 to 0.55	0.48 exacerbations per year Interval 0.33 to 0.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fluticasone 44 mcg n=127 Participants 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	Fluticasone 220 mcg n=127 Participants 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
Yellow Zone Asthma Symptoms	20 units on a scale Interval 17.0 to 24.0	23 units on a scale Interval 19.0 to 27.0

SECONDARY outcome

Timeframe: end of 48 week treatment period

Use of albuterol rescue medication during 7-day yellow zone episodes.

Outcome measures

Measure	Fluticasone 44 mcg n=127 Participants 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	Fluticasone 220 mcg n=127 Participants 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
Yellow Zone Albuterol Use	13 number of albuterol puffs Interval 11.0 to 16.0	15 number of albuterol puffs Interval 13.0 to 19.0

SECONDARY outcome

Timeframe: end of 48 week treatment period

Rate of emergency department (ED) or urgent care visits for asthma during the 48 week treatment period.

Outcome measures

Measure	Fluticasone 44 mcg n=127 Participants 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	Fluticasone 220 mcg n=127 Participants 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
Unscheduled Emergency Department (ED) or Urgent Care Visits for Asthma	0.47 visits per year Interval 0.31 to 0.72	0.64 visits per year Interval 0.42 to 0.96

SECONDARY outcome

Timeframe: end of 48 week treatment period

Number of participants hospitalized for asthma during the 48 week treatment period.

Outcome measures

Measure	Fluticasone 44 mcg n=127 Participants 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	Fluticasone 220 mcg n=127 Participants 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
Number of Participants Hospitalized for Asthma	0 Participants	4 Participants

Adverse Events

Fluticasone 44 mcg

Serious events: 1 serious events

Other events: 115 other events

Deaths: 0 deaths

Fluticasone 220 mcg

Serious events: 4 serious events

Other events: 111 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fluticasone 44 mcg n=127 participants at risk 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	Fluticasone 220 mcg n=127 participants at risk 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
Respiratory, thoracic and mediastinal disorders Asthma Exacerbation	0.00% 0/127 • 48 weeks	3.1% 4/127 • Number of events 4 • 48 weeks
Respiratory, thoracic and mediastinal disorders Hypertrophy Tonsils/Adenoids	0.79% 1/127 • Number of events 1 • 48 weeks	0.00% 0/127 • 48 weeks

Other adverse events

Measure	Fluticasone 44 mcg n=127 participants at risk 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	Fluticasone 220 mcg n=127 participants at risk 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
Nervous system disorders Otitis media	11.0% 14/127 • Number of events 17 • 48 weeks	11.0% 14/127 • Number of events 20 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute nasopharyngitis	36.2% 46/127 • Number of events 99 • 48 weeks	26.0% 33/127 • Number of events 57 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory tract infection	17.3% 22/127 • Number of events 39 • 48 weeks	16.5% 21/127 • Number of events 41 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute sinusitis	3.9% 5/127 • Number of events 6 • 48 weeks	5.5% 7/127 • Number of events 9 • 48 weeks
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	28.3% 36/127 • Number of events 62 • 48 weeks	22.0% 28/127 • Number of events 45 • 48 weeks
Infections and infestations Infectious enteritis	5.5% 7/127 • Number of events 8 • 48 weeks	4.7% 6/127 • Number of events 7 • 48 weeks
Infections and infestations Strep sore throat	3.9% 5/127 • Number of events 5 • 48 weeks	7.9% 10/127 • Number of events 16 • 48 weeks
General disorders Cough	22.8% 29/127 • Number of events 45 • 48 weeks	23.6% 30/127 • Number of events 49 • 48 weeks
General disorders Fever	18.9% 24/127 • Number of events 39 • 48 weeks	16.5% 21/127 • Number of events 28 • 48 weeks
General disorders Headache	11.8% 15/127 • Number of events 22 • 48 weeks	7.9% 10/127 • Number of events 12 • 48 weeks
General disorders Throat pain	3.9% 5/127 • Number of events 7 • 48 weeks	6.3% 8/127 • Number of events 8 • 48 weeks
General disorders Vomiting alone	6.3% 8/127 • Number of events 9 • 48 weeks	7.9% 10/127 • Number of events 14 • 48 weeks
Respiratory, thoracic and mediastinal disorders Wheezing	6.3% 8/127 • Number of events 11 • 48 weeks	4.7% 6/127 • Number of events 8 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute asthma attack	19.7% 25/127 • Number of events 32 • 48 weeks	23.6% 30/127 • Number of events 37 • 48 weeks

Additional Information

David Mauger, PhD

Penn State University Dept of Public Health Sciences

Phone: 717.531.3584

Email: dmauger@psu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place