Childhood Asthma Research and Education (CARE) Network Trial - Acute Intervention Management Strategies (AIMS)

Acute Intervention Management Strategies (AIMS) is a randomized, double-blind, double-dummy,
placebo-controlled parallel comparison study that will compare the effectiveness of three
treatments, when given at the onset of RTI-associated symptoms, in increasing the proportion
of symptom-free days over the entire treatment period of the 5- to 9-month study. There will
be a 2-week period to qualify and characterize participants, who at that time will have no
lower respiratory tract symptoms other than mild cough. A total of 244 participants will be
randomized to one of three treatment groups and followed for the remainder of the
fall-winter-early spring season. Participants will receive one of the following treatment
regimens for 7 days, at the first sign of RTI-associated symptoms: 1) active ICS plus
placebo LTRA plus albuterol inhalation treatments four times daily; 2) active LTRA plus
placebo ICS plus albuterol inhalation treatment four times daily; or 3) placebo ICS plus
placebo LTRA plus albuterol inhalation treatments four times daily.

Inclusion Criteria:

- Recurrent episodes (at least two) of wheezing in the context of a RTI, at least one
of which must be documented by a health care provider (parental report) over the 12
months prior to study entry, and of which one episode must have occurred within 6
months prior to study entry

- Either two episodes of '1,' OR two episodes of '2,' OR one episode of '1' AND one
episode of '2,' defined by the following:

1. Urgent care visit for acute wheezing (emergency department, urgent care center,
or unscheduled primary care physician office visit), which required treatment
with a bronchodilator, within 12 months prior to study entry

2. Episode of wheezing within 12 months prior to study entry, which required
treatment with oral corticosteroids not associated with a visit to a health care
provider, urgent care center, emergency department, or hospital

- Immunizations are up to date, including varicella (unless the patient has already had
clinical varicella)

- Willingness to provide informed consent by patient's parent or guardian

Exclusion Criteria:

- Use of more than six courses of systemic corticosteroids during the 12 months prior
to study entry

- More than two hospitalizations for wheezing illnesses within 12 months prior to study
entry

- Use of long-term controller medications for asthma (including inhaled
corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline) for 4
or more months (cumulative use) within 1 year prior to study entry

- Any use of long-term controller medications for asthma (including corticosteroids
[inhaled or oral], leukotriene modifiers, cromolyn/nedocromil, or theophylline)
within the 2 weeks prior to the enrollment visit

- Current treatment with antibiotics for diagnosed sinus disease

- Contraindication of use of systemic corticosteroids

- Prematurity (defined as birth before 36 weeks gestational age)

- Presence of lung disease other than asthma (e.g., cystic fibrosis and BPD)

- Presence of other significant medical illnesses (e.g., cardiac, liver,
gastrointestinal, or endocrine disease) that would place the patient at increased
risk

- Gastroesophageal reflux under medical therapy

- Immunodeficiency disorders

- History of respiratory failure requiring mechanical ventilation

- History of hypoxic seizure

- Inability to cooperate with nebulization therapy

- Inability to ingest the study drugs

- History of significant adverse reaction to any study medication ingredient

- Current participation, or participation in the month prior to study entry, in another
investigational drug study

- Evidence that the family may be unreliable, nonadherent, or likely to move from the
clinical center area before study completion

- Persistent symptomatic asthma, as defined as experiencing symptoms (i.e., nocturnal
cough, daytime cough, wheezing, difficulty breathing, or symptoms interfering with
activities) and/or requiring albuterol use on average 4 or more days per week in the
2-week observation period prior to the randomization visit

- The following scores, based on a 5-point scale with 5 representing very severe
symptoms (measured at randomization visit): score equal to or greater than one for
albuterol use, wheezing, difficulty breathing, nighttime cough, and asthma symptoms
interfering with activities; score greater than 2 for daytime cough on an average of
4 or more days/week during the 2-week observation period

- Failure to complete diary cards at expected levels (at least 80% of days) during the
observation period

- Use of long-term controller medications for asthma (e.g., corticosteroids [inhaled or
oral], leukotriene modifiers, cromolyn/nedocromil, or theophylline) during the 2-week
observation period