search
Back to results

Individualized Therapy For Asthma in Toddlers (INFANT)

Primary Purpose

Asthma, Wheezing

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
daily fluticasone propionate
Montelukast
as-needed fluticasone propionate
Sponsored by
Milton S. Hershey Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Asthma, Wheezing, Fluticasone, Montelukast, Preschool-age

Eligibility Criteria

12 Months - 59 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 12-59 months of age.
  • If the child is not currently taking long-term asthma controller therapy (meaning that the child has taken no inhaled corticosteroid or leukotriene receptor antagonist medication whatsoever over the past 6 months), then one of the following criteria must be met:

    • Daytime asthma symptoms more than two days per week (average over the past 4 weeks),
    • At least one nighttime awakening from asthma (over the past 4 weeks),
    • Two or more asthma exacerbations requiring systemic corticosteroids in the previous 6 months,
    • Four or more wheezing episodes in the previous 12 months.
  • If the child is currently taking long-term asthma controller therapy (meaning that the child has taken daily or intermittent/as-needed inhaled corticosteroid or leukotriene receptor antagonist over the past 6 months), then one of the following criteria must be met:

    • Taking inhaled corticosteroid or leukotriene receptor antagonist for more than 3 months (or more than 90 days) out of the previous 6 months (or 180 days),
    • Daytime asthma symptoms more than two days per week (average over the past 4 weeks),
    • More than one nighttime awakening from asthma (over the past 4 weeks),
    • Two or more asthma exacerbations requiring systemic corticosteroids in the previous 12 months,
    • Four or more wheezing episodes in the previous 12 months.
  • Up to date with immunizations, including varicella (unless the subject has already had clinical varicella).
  • Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

  • Allergic reaction to the study medications or any component of the study drugs, including (but not limited to) urticaria, rash, angioedema, or hypotension following delivery,
  • Chronic medical disorders that could interfere with drug metabolism/excretion (for instance chronic hepatic, biliary, or renal disease),
  • Chronic medical disorders that may increase the risk of drug-related injury, including (but not limited to):

    • Osteogenesis imperfecta (increased risk of bone demineralization/fracture with corticosteroid therapy),
    • Crohn's disease, ulcerative colitis, juvenile rheumatoid arthritis, clotting disorders, or Factor deficiency (increased risk of bleeding with corticosteroid therapy),
    • G6PD deficiency (increased risk of hemolytic anemia with acetaminophen use),
    • Phenylketonuria (potential for aspartame exposure with study interventions),
    • Seizure disorder treated with anticonvulsants (risk of acetaminophen toxicity with carbamazepine), or
    • History of clotting disorders or Factor deficiency (increased risk of bleeding with corticosteroids),
  • Co-morbid disorders associated with wheezing including (but not limited to) immune deficiency disorders, cystic fibrosis, aspiration, clinically-relevant gastroesophageal reflux, tracheomalacia, congenital airway anomalies (clefts, fistulas, slings, rings), bronchiectasis, bronchopulmonary dysplasia, and/or history of premature birth before 35 weeks gestation,
  • Significant developmental delay/failure to thrive, defined as 5th percentile for height and/or weight or crossing of two major percentile lines during the last year for age and sex,
  • History of a near-fatal asthma exacerbation requiring intubation or assisted ventilation,
  • No primary medical caregiver (e.g., a nurse practitioner, physician assistant, physician, or group medical practice such as a hospital-based clinic) whom the subject can contact for primary medical care,
  • Three or more hospitalizations in the previous 12 months for wheezing or respiratory illnesses,
  • Treatment with 5 or more courses of systemic corticosteroids (oral, intramuscular or intravenous) in the past 6 months,
  • Current use of higher than step 2 NAEPP asthma guideline therapy
  • If receiving allergy shots, change in the dose within the past 3 months.

Sites / Locations

  • University of Arizona College of Medicine
  • Children's Hospital & Research Center Oakland
  • UCSF Benioff Children's Hospital
  • National Jewish Health
  • Emory University
  • Rush University Medical Center/Stroger Hospital
  • Children's Memorial Hospital
  • Children's Hospital, Boston
  • St. Louis Children's Hospital
  • Rainbow Babies and Children's Hospital, Case Western Reserve University
  • Children's Hospital of Pittsburgh of UPMC
  • University of Virginia Health System
  • University of Wisconsin-Madison

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Crossover sequence 1

Crossover sequence 2

Crossover sequence 3

Crossover sequence 4

Crossover sequence 5

Crossover sequence 6

Arm 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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
May 23, 2012
Last Updated
January 27, 2017
Sponsor
Milton S. Hershey Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01606306
Brief Title
Individualized Therapy For Asthma in Toddlers
Acronym
INFANT
Official Title
Individualized Therapy For Asthma in Toddlers
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Milton S. Hershey Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The INFANT study will test whether, in preschool children 12-59 months of age with persistent asthma, the following Step 2 asthma therapies will provide similar degrees of asthma control: Daily inhaled corticosteroid (ICS) treatment, Daily leukotriene receptor antagonist (LTRA) treatment, and As-needed ICS plus short-acting beta agonist (as-needed ICS/SABA) rescue treatment.
Detailed Description
INFANT is a double-blind, randomized clinical trial in which all participants will receive each of the three therapies for 16 weeks by means of a cross-over study design. INFANT aims to determine whether individual children respond better to one treatment than another and, if so, whether those children can be identified by phenotypic characteristics or selected biomarkers. In this regard the INFANT study is expected to address critical gaps in current asthma management guidelines. Ultimately, the findings from this study are expected to help clarify treatment modalities for this population of young preschool children who are extremely difficult to treat.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Wheezing
Keywords
Asthma, Wheezing, Fluticasone, Montelukast, Preschool-age

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Crossover sequence 1
Arm Type
Experimental
Arm Description
daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate
Arm Title
Crossover sequence 2
Arm Type
Experimental
Arm Description
daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast
Arm Title
Crossover sequence 3
Arm Type
Experimental
Arm Description
daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate
Arm Title
Crossover sequence 4
Arm Type
Experimental
Arm Description
daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate
Arm Title
Crossover sequence 5
Arm Type
Experimental
Arm Description
as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast
Arm Title
Crossover sequence 6
Arm Type
Experimental
Arm Description
as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate
Intervention Type
Drug
Intervention Name(s)
daily fluticasone propionate
Intervention Description
Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily
Intervention Type
Drug
Intervention Name(s)
Montelukast
Intervention Description
Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening
Intervention Type
Drug
Intervention Name(s)
as-needed fluticasone propionate
Intervention Description
Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms
Primary Outcome Measure Information:
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 12-59 months of age. If the child is not currently taking long-term asthma controller therapy (meaning that the child has taken no inhaled corticosteroid or leukotriene receptor antagonist medication whatsoever over the past 6 months), then one of the following criteria must be met: Daytime asthma symptoms more than two days per week (average over the past 4 weeks), At least one nighttime awakening from asthma (over the past 4 weeks), Two or more asthma exacerbations requiring systemic corticosteroids in the previous 6 months, Four or more wheezing episodes in the previous 12 months. If the child is currently taking long-term asthma controller therapy (meaning that the child has taken daily or intermittent/as-needed inhaled corticosteroid or leukotriene receptor antagonist over the past 6 months), then one of the following criteria must be met: Taking inhaled corticosteroid or leukotriene receptor antagonist for more than 3 months (or more than 90 days) out of the previous 6 months (or 180 days), Daytime asthma symptoms more than two days per week (average over the past 4 weeks), More than one nighttime awakening from asthma (over the past 4 weeks), Two or more asthma exacerbations requiring systemic corticosteroids in the previous 12 months, Four or more wheezing episodes in the previous 12 months. Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). Willingness to provide informed consent by the child's parent or guardian. Exclusion Criteria: Allergic reaction to the study medications or any component of the study drugs, including (but not limited to) urticaria, rash, angioedema, or hypotension following delivery, Chronic medical disorders that could interfere with drug metabolism/excretion (for instance chronic hepatic, biliary, or renal disease), Chronic medical disorders that may increase the risk of drug-related injury, including (but not limited to): Osteogenesis imperfecta (increased risk of bone demineralization/fracture with corticosteroid therapy), Crohn's disease, ulcerative colitis, juvenile rheumatoid arthritis, clotting disorders, or Factor deficiency (increased risk of bleeding with corticosteroid therapy), G6PD deficiency (increased risk of hemolytic anemia with acetaminophen use), Phenylketonuria (potential for aspartame exposure with study interventions), Seizure disorder treated with anticonvulsants (risk of acetaminophen toxicity with carbamazepine), or History of clotting disorders or Factor deficiency (increased risk of bleeding with corticosteroids), Co-morbid disorders associated with wheezing including (but not limited to) immune deficiency disorders, cystic fibrosis, aspiration, clinically-relevant gastroesophageal reflux, tracheomalacia, congenital airway anomalies (clefts, fistulas, slings, rings), bronchiectasis, bronchopulmonary dysplasia, and/or history of premature birth before 35 weeks gestation, Significant developmental delay/failure to thrive, defined as 5th percentile for height and/or weight or crossing of two major percentile lines during the last year for age and sex, History of a near-fatal asthma exacerbation requiring intubation or assisted ventilation, No primary medical caregiver (e.g., a nurse practitioner, physician assistant, physician, or group medical practice such as a hospital-based clinic) whom the subject can contact for primary medical care, Three or more hospitalizations in the previous 12 months for wheezing or respiratory illnesses, Treatment with 5 or more courses of systemic corticosteroids (oral, intramuscular or intravenous) in the past 6 months, Current use of higher than step 2 NAEPP asthma guideline therapy If receiving allergy shots, change in the dose within the past 3 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William B Busse, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Study Chair
Facility Information:
Facility Name
University of Arizona College of Medicine
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Children's Hospital & Research Center Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
UCSF Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center/Stroger Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Children's Hospital, Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
St. Louis Children's Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Rainbow Babies and Children's Hospital, Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
University of Wisconsin-Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27777180
Citation
Fitzpatrick AM, Jackson DJ, Mauger DT, Boehmer SJ, Phipatanakul W, Sheehan WJ, Moy JN, Paul IM, Bacharier LB, Cabana MD, Covar R, Holguin F, Lemanske RF Jr, Martinez FD, Pongracic JA, Beigelman A, Baxi SN, Benson M, Blake K, Chmiel JF, Daines CL, Daines MO, Gaffin JM, Gentile DA, Gower WA, Israel E, Kumar HV, Lang JE, Lazarus SC, Lima JJ, Ly N, Marbin J, Morgan W, Myers RE, Olin JT, Peters SP, Raissy HH, Robison RG, Ross K, Sorkness CA, Thyne SM, Szefler SJ; NIH/NHLBI AsthmaNet. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016 Dec;138(6):1608-1618.e12. doi: 10.1016/j.jaci.2016.09.028. Epub 2016 Oct 21.
Results Reference
derived

Learn more about this trial

Individualized Therapy For Asthma in Toddlers

We'll reach out to this number within 24 hrs