Individualized Therapy For Asthma in Toddlers
Condition: Asthma; Wheezing
MeSH terms: Asthma; Respiratory Sounds
Intervention: daily fluticasone propionate; Montelukast; as-needed fluticasone propionate
Intervention description: Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily; Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening; Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms
Intervention MeSH terms: Fluticasone; Xhance; Montelukast
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 300.0
Sex: All
Minimum age: 12 Months
Maximum age: 59 Months
Healthy volunteers: No
Keywords: Asthma; Wheezing; Fluticasone; Montelukast; Preschool-age

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.
    

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.