Clinical trial NCT01606306: Individualized Therapy For Asthma in Toddlers
Official title: Individualized Therapy For Asthma in Toddlers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Wheezing
Keywords: Asthma
Wheezing
Fluticasone
Montelukast
Preschool-age
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-05-25
Enrollment: 300
Sex: ALL
Minimum age (years): 12
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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:

1. Daily inhaled corticosteroid (ICS) treatment,
2. Daily leukotriene receptor antagonist (LTRA) treatment, and
3. 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.

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.

Primary outcomes:
measure: 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.
timeFrame: The last 14 weeks of each 16-week treatment period
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center/Stroger Hospital
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Children's Hospital, Boston
state: Massachusetts
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital, Case Western Reserve University
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: William B Busse, MD
role: STUDY_CHAIR
References:
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.