Treatment of Preschool Children With Upper Respiratory Tract Illnesses Using Azythromycin and Lower Respiratory Tract Symptoms Using Oral Corticosteroids.
Condition: Asthma; Wheezing
MeSH terms: Respiratory Sounds
Intervention: Azithromycin; Prednisolone; Placebo Azithromycin; Placebo Prednisolone
Intervention description: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day; Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day; Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day; Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Intervention MeSH terms: Azithromycin; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 607.0
Sex: All
Minimum age: 12 Months
Maximum age: 71 Months
Healthy volunteers: No
Keywords: Asthma; Wheezing; Respiratory Tract Illness; Azythromycin; Prednisolone; Preschool-age

Summary:

      This protocol is comprised of two separate, but linked, clinical trials for treating
      preschool-aged children with recurrent severe episodes of wheezing. The first study (APRIL)
      will try to prevent wheezing illness from developing using azithromycin. If a wheezing
      illness does occur, the second trial (OCELOT) will try to decrease the severity of symptoms
      using oral corticosteroids.
    

Eligibility criteria:

        Inclusion Criteria:

          -  12-71 months of age.

          -  Recurrent significant wheezing in the past year (any of the following):

               -  >3 episodes, ≥1 of which was clinically significant*; OR

               -  >2 clinically significant* episodes; OR

               -  >4 months of daily controller therapy AND >1 clinically significant* episode.

               -  * Clinically significant episode: requiring any of the following: (1) systemic
                  corticosteroids (oral or injectable), (2) unscheduled physician office visit, (3)
                  ED visit, (4) urgent care visit, or (5) hospitalization.

          -  Up to date with immunizations, including varicella (unless the subject has already had
             clinical varicella). If the subject needs varicella vaccine, this will be arranged
             with the primary care physician and must be received prior to randomization.

          -  Willingness to provide informed consent by the child's parent or guardian.

        Exclusion Criteria:

        Participants who meet any of the following criteria are NOT eligible for enrollment, but
        may be re-enrolled if these exclusion criteria are resolved:

          -  >4 courses of systemic corticosteroids in past 12 months.

          -  More than 1 hospitalization for wheezing illnesses within the preceding 12 months.

          -  Use of long-term controller medications for asthma, including inhaled corticosteroids,
             leukotriene modifiers, cromolyn/nedocromil, or theophylline for more than 8 months
             (cumulative use) in the past 12 months.

          -  Current use of higher than step 2 NAEPP asthma guideline therapy (e.g. medium-high
             dose ICS alone or combination therapy of low-medium-high dose ICS + LABA, montelukast,
             theophylline or cromolyn). NOTE: children who have evidence of well-controlled
             symptoms immediately preceding study entry while receiving Step 2 controller therapy
             (presence of self-reported symptoms on average no more than 2 times per week and less
             than 2 nights per month of nocturnal awakenings, requiring albuterol, during the 4
             weeks preceding visit 1) may be enrolled and will have their controller therapy
             discontinued upon study entry.

          -  Use of OCS in the past 2 weeks.

          -  Daily symptoms or >2 nocturnal awakenings, requiring albuterol, on average in the last
             2 weeks.

          -  Use of antibiotics in the past month.

          -  Current treatment with antibiotics for diagnosed sinus disease.

          -  Participation presently or in the past month in another investigational drug trial.

          -  Evidence that the family may be unreliable or nonadherent, or may move from the
             clinical center area before trial completion.

          -  Contraindication of use of systemic corticosteroids or azithromycin.

          -  Clinically relevant gastroesophageal reflux.

          -  Concurrent medical conditions other than asthma that are likely to require oral or
             injectable corticosteroids during the study.

          -  If receiving allergy shots, change in dose within the past 3 months.

        Participants who meet any of the following criteria are NOT eligible for enrollment, and
        may not be re-enrolled:

          -  Gestation less than late preterm as defined as birth before 34 weeks gestational age.

          -  Presence of lung disease other than asthma, such as cystic fibrosis and BPD.
             Evaluation during the screening process will assure that an adequate evaluation of
             other lung diseases has been performed.

          -  Presence of other significant medical illnesses (cardiac, liver, gastrointestinal,
             endocrine) that would place the study subject at increased risk of participating in
             the study.

          -  Immunodeficiency disorders.

          -  History of respiratory failure requiring mechanical ventilation.

          -  History of hypoxic seizure.

          -  History of significant adverse reaction to any study medication ingredient.

          -  The child has significant developmental delay/failure to thrive, defined as crossing
             of two major percentile lines during the last year for age and gender. If a child
             plots less than the 10th percentile for age and gender, a growth chart for the
             previous year will be obtained from the child's primary care provider.