Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Individualized Therapy For Asthma in Toddlers (INFANT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01606306
Recruitment Status : Completed
First Posted : May 25, 2012
Results First Posted : March 16, 2017
Last Update Posted : March 16, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
dave mauger, Milton S. Hershey Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Asthma
Wheezing
Interventions Drug: daily fluticasone propionate
Drug: Montelukast
Drug: as-needed fluticasone propionate
Enrollment 300
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Crossover Sequence 1 Crossover Sequence 2 Crossover Sequence 3 Crossover Sequence 4 Crossover Sequence 5 Crossover Sequence 6
Hide Arm/Group Description daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate
Period Title: Overall Study
Started 50 49 51 51 52 47
Completed First Treatment Period 43 47 47 45 47 44
Completed Second Treatment Period 41 38 43 44 46 41
Completed Third Treatment Period 35 39 37 38 41 36
Completed 35 39 37 38 41 36
Not Completed 15 10 14 13 11 11
Reason Not Completed
Lack of Efficacy             2             1             4             4             1             2
Adverse Event             1             0             1             1             2             0
Lost to Follow-up             7             4             5             4             3             5
Withdrawal by Subject             4             3             4             4             5             4
Physician Decision             1             2             0             0             0             0
Arm/Group Title Crossover Sequence 1 Crossover Sequence 2 Crossover Sequence 3 Crossover Sequence 4 Crossover Sequence 5 Crossover Sequence 6 Total
Hide Arm/Group Description daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate Total of all reporting groups
Overall Number of Baseline Participants 50 49 51 51 52 47 300
Hide Baseline Analysis Population Description
All randomized participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
<=18 years
50
 100.0%
49
 100.0%
51
 100.0%
51
 100.0%
52
 100.0%
47
 100.0%
300
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
38.3  (13.6) 40.7  (12.4) 38.7  (11.6) 38.6  (15.1) 41.7  (12.7) 41.2  (14.0) 39.9  (13.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Female
20
  40.0%
20
  40.8%
19
  37.3%
21
  41.2%
18
  34.6%
23
  48.9%
121
  40.3%
Male
30
  60.0%
29
  59.2%
32
  62.7%
30
  58.8%
34
  65.4%
24
  51.1%
179
  59.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Hispanic or Latino
17
  34.0%
12
  24.5%
10
  19.6%
11
  21.6%
12
  23.1%
10
  21.3%
72
  24.0%
Not Hispanic or Latino
33
  66.0%
37
  75.5%
41
  80.4%
40
  78.4%
40
  76.9%
37
  78.7%
228
  76.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
American Indian or Alaska Native
1
   2.0%
1
   2.0%
0
   0.0%
2
   3.9%
0
   0.0%
1
   2.1%
5
   1.7%
Asian
2
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.7%
Native Hawaiian or Other Pacific Islander
1
   2.0%
0
   0.0%
0
   0.0%
1
   2.0%
1
   1.9%
0
   0.0%
3
   1.0%
Black or African American
11
  22.0%
15
  30.6%
20
  39.2%
13
  25.5%
20
  38.5%
18
  38.3%
97
  32.3%
White
25
  50.0%
27
  55.1%
24
  47.1%
30
  58.8%
21
  40.4%
21
  44.7%
148
  49.3%
More than one race
10
  20.0%
6
  12.2%
7
  13.7%
5
   9.8%
10
  19.2%
7
  14.9%
45
  15.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
50 49 51 51 52 47 300
Parental Asthma  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Present 30 29 29 32 35 23 178
Not Present 20 20 22 19 17 24 122
Systemic corticosteroids in past 12 monts  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Used 37 35 37 40 39 36 224
Not used 13 14 14 11 13 11 76
Hospitalized in past 12 months  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Hospitalized 9 14 11 6 13 12 65
Not hospitalized 41 35 40 45 39 35 235
Allergen Test  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Positive test 18 20 20 21 25 17 121
Negative test 32 29 31 30 27 30 179
Eczema  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
Present 21 28 27 28 26 30 160
Not Present 29 21 24 23 26 17 140
Blood eosinophils  
Median (Inter-Quartile Range)
Unit of measure:  Number of cells per micro-liter
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
183
(111 to 435)
234
(153 to 572)
258
(133 to 460)
255
(175 to 457)
308
(184 to 496)
310
(182 to 536)
258
(158 to 492)
Serum IgE  
Median (Inter-Quartile Range)
Unit of measure:  International units per liter
Number Analyzed 50 participants 49 participants 51 participants 51 participants 52 participants 47 participants 300 participants
67
(25 to 212)
106.5
(22 to 463)
64
(21 to 141)
64
(31 to 143)
87
(19 to 237)
84
(19 to 348)
70
(22 to 208)
1.Primary Outcome
Title 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.
Hide Description 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.
Time Frame The last 14 weeks of each 16-week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Differential response was determined in children completing at least two treatment periods and at least 50% of the daily diary entries for each period.
Arm/Group Title All Evaluable Participants
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 230
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
Non-differential responders
.26
(.26 to .26)
Responded best to daily ICS
.40
(.33 to .47)
Responded best to daily LTRA
.18
(.13 to .23)
Responded best to as-needed ICS
.16
(.11 to .21)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Evaluable Participants
Comments The primary analysis tested the null hypothesis of all three treatments having equal probability to yield the best response as defined by the criteria defining the primary outcome. A sample size of 300 participants was selected to test the primary null hypothesis of all three treatments having equal probability (one-third) to yield the best response with statistical power of at least 0.90 if any one of the three treatments actually has probability of at least one-half to yield the best response.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Rank-ordered logistic regression (ROLR) was used to model the probability of best response for each treatment and bootstrapping was used to calculate confidence intervals.
Method rank-order logistic regression
Comments ROLR is in the class of Discrete Choice models, which seek to estimate the probability that an individual responds best to a specific treatments.
Other Statistical Analysis The probabilistic construct of the Discrete Choice (DC) model does not reflect individual behavior that is intrinsically probabilistic, but rather population heterogeneity. DC models rely on stochastic assumptions to account for unobserved factors related to the treatments themselves and to characteristics of study participants. Specifically, that each treatment has an underlying utility that may differ from one individual to another. Mathematically, these utilities are represented by U_t, where t denotes the treatment. Utility can be thought of as a latent variable quantifying treatment response where higher values indicate better response. The U_t can be used to find the probability (P) of best response for each treatment by the following equation: P_t = exp(U_t) / [exp(U_A) + exp(U_B) + exp(U_C)], where A, B, and C, denote the three study treatments. The primary analysis tested whether the three treatments have equal utility and, thus, equal probability of best response.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Daily ICS As-needed ICS Daily LTRA
Hide Arm/Group Description Daily inhaled corticosteroid (ICS) treatment As-needed ICS plus short-acting beta agonist (as-needed ICS/SABA) rescue treatment. Daily leukotriene receptor antagonist (LTRA) treatment
All-Cause Mortality
Daily ICS As-needed ICS Daily LTRA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Daily ICS As-needed ICS Daily LTRA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/300 (0.67%)      8/300 (2.67%)      8/300 (2.67%)    
Gastrointestinal disorders       
Constipation  0/300 (0.00%)  0 1/300 (0.33%)  1 0/300 (0.00%)  0
Injury, poisoning and procedural complications       
Simple laceration  1/300 (0.33%)  1 0/300 (0.00%)  0 0/300 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Influenza  1/300 (0.33%)  1 0/300 (0.00%)  0 0/300 (0.00%)  0
Penumonia  0/300 (0.00%)  0 1/300 (0.33%)  1 0/300 (0.00%)  0
asthma exacerbation  0/300 (0.00%)  0 4/300 (1.33%)  4 8/300 (2.67%)  8
bronchitis  0/300 (0.00%)  0 1/300 (0.33%)  1 0/300 (0.00%)  0
Surgical and medical procedures       
tonsilitis  0/300 (0.00%)  0 1/300 (0.33%)  1 0/300 (0.00%)  0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daily ICS As-needed ICS Daily LTRA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   212/300 (70.67%)      206/300 (68.67%)      212/300 (70.67%)    
Ear and labyrinth disorders       
Otitis media  22/300 (7.33%)  27 24/300 (8.00%)  27 28/300 (9.33%)  29
General disorders       
Fever  100/300 (33.33%)  127 89/300 (29.67%)  111 109/300 (36.33%)  146
Headache  16/300 (5.33%)  20 14/300 (4.67%)  17 11/300 (3.67%)  17
Respiratory, thoracic and mediastinal disorders       
Acute upper respiratory tract infection  39/300 (13.00%)  45 41/300 (13.67%)  53 54/300 (18.00%)  65
Allergic rhinitis  11/300 (3.67%)  15 16/300 (5.33%)  21 26/300 (8.67%)  36
Cough  27/300 (9.00%)  31 35/300 (11.67%)  42 26/300 (8.67%)  32
Wheezing  41/300 (13.67%)  47 59/300 (19.67%)  70 68/300 (22.67%)  84
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Mauger, PhD
Organization: Penn State University Dept of Public Health Sciences
Phone: 717.573.0336
EMail: dmauger@psu.edu
Layout table for additonal information
Responsible Party: dave mauger, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01606306    
Other Study ID Numbers: AsthmaNet 004
1U10HL098115 ( U.S. NIH Grant/Contract )
First Submitted: May 23, 2012
First Posted: May 25, 2012
Results First Submitted: September 15, 2016
Results First Posted: March 16, 2017
Last Update Posted: March 16, 2017