Individualized Therapy For Asthma in Toddlers

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.

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.