Individualized Therapy For Asthma in Toddlers (INFANT)

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.

• Asthma
• Wheezing

• Drug: daily fluticasone propionate
  Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily
• Drug: Montelukast
  Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening
• Drug: as-needed fluticasone propionate
  Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

• Experimental: Crossover sequence 1
  daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate
  Interventions:

  • Drug: daily fluticasone propionate
  • Drug: Montelukast
  • Drug: as-needed fluticasone propionate
• Experimental: Crossover sequence 2
  daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast
  Interventions:

  • Drug: daily fluticasone propionate
  • Drug: Montelukast
  • Drug: as-needed fluticasone propionate
• Experimental: Crossover sequence 3
  daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate
  Interventions:

  • Drug: daily fluticasone propionate
  • Drug: Montelukast
  • Drug: as-needed fluticasone propionate
• Experimental: Crossover sequence 4
  daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate
  Interventions:

  • Drug: daily fluticasone propionate
  • Drug: Montelukast
  • Drug: as-needed fluticasone propionate
• Experimental: Crossover sequence 5
  as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast
  Interventions:

  • Drug: daily fluticasone propionate
  • Drug: Montelukast
  • Drug: as-needed fluticasone propionate
• Experimental: Crossover sequence 6
  as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate
  Interventions:

  • Drug: daily fluticasone propionate
  • Drug: Montelukast
  • Drug: as-needed fluticasone propionate

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.