Trial Outcomes & Findings for Individualized Therapy For Asthma in Toddlers (NCT NCT01606306)
NCT ID: NCT01606306
Last Updated: 2017-03-16
Results Overview
The primary outcome was differential response to the three therapies on the basis of fixed threshold criteria for the following asthma control measures, which encompassed domains of risk and impairment: the time from the start of the treatment period to an asthma exacerbation treated with systemic corticosteroids, and the annualized number of asthma control days (ACDs) from within that period. ACDs were defined as full calendar days without symptoms, rescue medication use, or unscheduled healthcare visits. Children were defined as differential responders if, first, the time to an asthma exacerbation was at least four weeks longer, or second, if the number of annualized ACDs was at least 31 days more for one treatment than another, in that order. If neither threshold was met, the participant was considered a non differential responder. Differential response was determined in children completing at least two treatment periods and at least 50% of the daily diary entries for each period.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
300 participants
Primary outcome timeframe
The last 14 weeks of each 16-week treatment period
Results posted on
2017-03-16
Participant Flow
Participant milestones
| Measure |
Crossover Sequence 1
daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate
|
Crossover Sequence 2
daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast
|
Crossover Sequence 3
daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate
|
Crossover Sequence 4
daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate
|
Crossover Sequence 5
as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast
|
Crossover Sequence 6
as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
50
|
49
|
51
|
51
|
52
|
47
|
|
Overall Study
Completed First Treatment Period
|
43
|
47
|
47
|
45
|
47
|
44
|
|
Overall Study
Completed Second Treatment Period
|
41
|
38
|
43
|
44
|
46
|
41
|
|
Overall Study
Completed Third Treatment Period
|
35
|
39
|
37
|
38
|
41
|
36
|
|
Overall Study
COMPLETED
|
35
|
39
|
37
|
38
|
41
|
36
|
|
Overall Study
NOT COMPLETED
|
15
|
10
|
14
|
13
|
11
|
11
|
Reasons for withdrawal
| Measure |
Crossover Sequence 1
daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate
|
Crossover Sequence 2
daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast
|
Crossover Sequence 3
daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate
|
Crossover Sequence 4
daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate
|
Crossover Sequence 5
as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast
|
Crossover Sequence 6
as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate
|
|---|---|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
4
|
4
|
1
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
1
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
7
|
4
|
5
|
4
|
3
|
5
|
|
Overall Study
Withdrawal by Subject
|
4
|
3
|
4
|
4
|
5
|
4
|
|
Overall Study
Physician Decision
|
1
|
2
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Individualized Therapy For Asthma in Toddlers
Baseline characteristics by cohort
| Measure |
Crossover Sequence 1
n=50 Participants
daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate
|
Crossover Sequence 2
n=49 Participants
daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast
|
Crossover Sequence 3
n=51 Participants
daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate
|
Crossover Sequence 4
n=51 Participants
daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate
|
Crossover Sequence 5
n=52 Participants
as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast
|
Crossover Sequence 6
n=47 Participants
as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate
|
Total
n=300 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Blood eosinophils
|
183 number of cells per micro-liter
n=5 Participants
|
234 number of cells per micro-liter
n=7 Participants
|
258 number of cells per micro-liter
n=5 Participants
|
255 number of cells per micro-liter
n=4 Participants
|
308 number of cells per micro-liter
n=21 Participants
|
310 number of cells per micro-liter
n=10 Participants
|
258 number of cells per micro-liter
n=115 Participants
|
|
Serum IgE
|
67 international units per liter
n=5 Participants
|
106.5 international units per liter
n=7 Participants
|
64 international units per liter
n=5 Participants
|
64 international units per liter
n=4 Participants
|
87 international units per liter
n=21 Participants
|
84 international units per liter
n=10 Participants
|
70 international units per liter
n=115 Participants
|
|
Age, Categorical
<=18 years
|
50 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
47 Participants
n=10 Participants
|
300 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Continuous
|
38.3 months
STANDARD_DEVIATION 13.6 • n=5 Participants
|
40.7 months
STANDARD_DEVIATION 12.4 • n=7 Participants
|
38.7 months
STANDARD_DEVIATION 11.6 • n=5 Participants
|
38.6 months
STANDARD_DEVIATION 15.1 • n=4 Participants
|
41.7 months
STANDARD_DEVIATION 12.7 • n=21 Participants
|
41.2 months
STANDARD_DEVIATION 14.0 • n=10 Participants
|
39.9 months
STANDARD_DEVIATION 13.2 • n=115 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
23 Participants
n=10 Participants
|
121 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
24 Participants
n=10 Participants
|
179 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
17 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
72 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
40 Participants
n=21 Participants
|
37 Participants
n=10 Participants
|
228 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
18 Participants
n=10 Participants
|
97 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
21 Participants
n=10 Participants
|
148 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
45 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
49 participants
n=7 Participants
|
51 participants
n=5 Participants
|
51 participants
n=4 Participants
|
52 participants
n=21 Participants
|
47 participants
n=10 Participants
|
300 participants
n=115 Participants
|
|
Parental Asthma
Present
|
30 participants
n=5 Participants
|
29 participants
n=7 Participants
|
29 participants
n=5 Participants
|
32 participants
n=4 Participants
|
35 participants
n=21 Participants
|
23 participants
n=10 Participants
|
178 participants
n=115 Participants
|
|
Parental Asthma
Not Present
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
22 participants
n=5 Participants
|
19 participants
n=4 Participants
|
17 participants
n=21 Participants
|
24 participants
n=10 Participants
|
122 participants
n=115 Participants
|
|
Systemic corticosteroids in past 12 monts
Used
|
37 participants
n=5 Participants
|
35 participants
n=7 Participants
|
37 participants
n=5 Participants
|
40 participants
n=4 Participants
|
39 participants
n=21 Participants
|
36 participants
n=10 Participants
|
224 participants
n=115 Participants
|
|
Systemic corticosteroids in past 12 monts
Not used
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
14 participants
n=5 Participants
|
11 participants
n=4 Participants
|
13 participants
n=21 Participants
|
11 participants
n=10 Participants
|
76 participants
n=115 Participants
|
|
Hospitalized in past 12 months
Hospitalized
|
9 participants
n=5 Participants
|
14 participants
n=7 Participants
|
11 participants
n=5 Participants
|
6 participants
n=4 Participants
|
13 participants
n=21 Participants
|
12 participants
n=10 Participants
|
65 participants
n=115 Participants
|
|
Hospitalized in past 12 months
Not hospitalized
|
41 participants
n=5 Participants
|
35 participants
n=7 Participants
|
40 participants
n=5 Participants
|
45 participants
n=4 Participants
|
39 participants
n=21 Participants
|
35 participants
n=10 Participants
|
235 participants
n=115 Participants
|
|
Allergen Test
Positive test
|
18 participants
n=5 Participants
|
20 participants
n=7 Participants
|
20 participants
n=5 Participants
|
21 participants
n=4 Participants
|
25 participants
n=21 Participants
|
17 participants
n=10 Participants
|
121 participants
n=115 Participants
|
|
Allergen Test
Negative test
|
32 participants
n=5 Participants
|
29 participants
n=7 Participants
|
31 participants
n=5 Participants
|
30 participants
n=4 Participants
|
27 participants
n=21 Participants
|
30 participants
n=10 Participants
|
179 participants
n=115 Participants
|
|
Eczema
Present
|
21 participants
n=5 Participants
|
28 participants
n=7 Participants
|
27 participants
n=5 Participants
|
28 participants
n=4 Participants
|
26 participants
n=21 Participants
|
30 participants
n=10 Participants
|
160 participants
n=115 Participants
|
|
Eczema
Not Present
|
29 participants
n=5 Participants
|
21 participants
n=7 Participants
|
24 participants
n=5 Participants
|
23 participants
n=4 Participants
|
26 participants
n=21 Participants
|
17 participants
n=10 Participants
|
140 participants
n=115 Participants
|
PRIMARY outcome
Timeframe: The last 14 weeks of each 16-week treatment periodPopulation: Differential response was determined in children completing at least two treatment periods and at least 50% of the daily diary entries for each period.
The primary outcome was differential response to the three therapies on the basis of fixed threshold criteria for the following asthma control measures, which encompassed domains of risk and impairment: the time from the start of the treatment period to an asthma exacerbation treated with systemic corticosteroids, and the annualized number of asthma control days (ACDs) from within that period. ACDs were defined as full calendar days without symptoms, rescue medication use, or unscheduled healthcare visits. Children were defined as differential responders if, first, the time to an asthma exacerbation was at least four weeks longer, or second, if the number of annualized ACDs was at least 31 days more for one treatment than another, in that order. If neither threshold was met, the participant was considered a non differential responder. Differential response was determined in children completing at least two treatment periods and at least 50% of the daily diary entries for each period.
Outcome measures
| Measure |
All Evaluable Participants
n=230 Participants
Differential response was determined in children completing at least two treatment periods and at least 50% of the daily diary entries for each period. Because placebo washouts were not performed, the data collected during the first two weeks of each period were not included in the analysis of ACDs. Days with missing diary data were also excluded from ACD determination.
|
|---|---|
|
Differential Response to the Three Therapies Based on Fixed Threshold Criteria for the Following Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations and Asthma Control Days.
Non-differential responders
|
.26 probability
Interval 0.26 to 0.26
|
|
Differential Response to the Three Therapies Based on Fixed Threshold Criteria for the Following Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations and Asthma Control Days.
Responded best to daily ICS
|
.40 probability
Interval 0.33 to 0.47
|
|
Differential Response to the Three Therapies Based on Fixed Threshold Criteria for the Following Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations and Asthma Control Days.
Responded best to daily LTRA
|
.18 probability
Interval 0.13 to 0.23
|
|
Differential Response to the Three Therapies Based on Fixed Threshold Criteria for the Following Asthma Control Measures: Use of Oral Prednisone for Acute Asthma Exacerbations and Asthma Control Days.
Responded best to as-needed ICS
|
.16 probability
Interval 0.11 to 0.21
|
Adverse Events
Daily ICS
Serious events: 2 serious events
Other events: 212 other events
Deaths: 0 deaths
As-needed ICS
Serious events: 8 serious events
Other events: 206 other events
Deaths: 0 deaths
Daily LTRA
Serious events: 8 serious events
Other events: 212 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Daily ICS
n=300 participants at risk
Daily inhaled corticosteroid (ICS) treatment
|
As-needed ICS
n=300 participants at risk
As-needed ICS plus short-acting beta agonist (as-needed ICS/SABA) rescue treatment.
|
Daily LTRA
n=300 participants at risk
Daily leukotriene receptor antagonist (LTRA) treatment
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/300
|
0.33%
1/300 • Number of events 1
|
0.00%
0/300
|
|
Injury, poisoning and procedural complications
Simple laceration
|
0.33%
1/300 • Number of events 1
|
0.00%
0/300
|
0.00%
0/300
|
|
Respiratory, thoracic and mediastinal disorders
Influenza
|
0.33%
1/300 • Number of events 1
|
0.00%
0/300
|
0.00%
0/300
|
|
Respiratory, thoracic and mediastinal disorders
Penumonia
|
0.00%
0/300
|
0.33%
1/300 • Number of events 1
|
0.00%
0/300
|
|
Respiratory, thoracic and mediastinal disorders
asthma exacerbation
|
0.00%
0/300
|
1.3%
4/300 • Number of events 4
|
2.7%
8/300 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
bronchitis
|
0.00%
0/300
|
0.33%
1/300 • Number of events 1
|
0.00%
0/300
|
|
Surgical and medical procedures
tonsilitis
|
0.00%
0/300
|
0.33%
1/300 • Number of events 1
|
0.00%
0/300
|
Other adverse events
| Measure |
Daily ICS
n=300 participants at risk
Daily inhaled corticosteroid (ICS) treatment
|
As-needed ICS
n=300 participants at risk
As-needed ICS plus short-acting beta agonist (as-needed ICS/SABA) rescue treatment.
|
Daily LTRA
n=300 participants at risk
Daily leukotriene receptor antagonist (LTRA) treatment
|
|---|---|---|---|
|
Ear and labyrinth disorders
Otitis media
|
7.3%
22/300 • Number of events 27
|
8.0%
24/300 • Number of events 27
|
9.3%
28/300 • Number of events 29
|
|
General disorders
Fever
|
33.3%
100/300 • Number of events 127
|
29.7%
89/300 • Number of events 111
|
36.3%
109/300 • Number of events 146
|
|
General disorders
Headache
|
5.3%
16/300 • Number of events 20
|
4.7%
14/300 • Number of events 17
|
3.7%
11/300 • Number of events 17
|
|
Respiratory, thoracic and mediastinal disorders
Acute upper respiratory tract infection
|
13.0%
39/300 • Number of events 45
|
13.7%
41/300 • Number of events 53
|
18.0%
54/300 • Number of events 65
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
3.7%
11/300 • Number of events 15
|
5.3%
16/300 • Number of events 21
|
8.7%
26/300 • Number of events 36
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.0%
27/300 • Number of events 31
|
11.7%
35/300 • Number of events 42
|
8.7%
26/300 • Number of events 32
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
13.7%
41/300 • Number of events 47
|
19.7%
59/300 • Number of events 70
|
22.7%
68/300 • Number of events 84
|
Additional Information
David Mauger, PhD
Penn State University Dept of Public Health Sciences
Phone: 717.573.0336
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place