Azithromycin to Prevent Wheezing Following Severe Respiratory Syncytial Virus (RSV) Bronchiolitis
Condition: RSV Bronchiolitis
MeSH terms: Bronchiolitis; Respiratory Sounds
Intervention: Azithromycin; Placebo
Intervention description: Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days.
Intervention MeSH terms: Azithromycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 1 Month
Maximum age: 18 Months
Healthy volunteers: No

Summary:

      This trial is a proof-of-concept pilot study aim to investigate the biologic and clinical
      effects of early azithromycin treatment in children hospitalized with Respiratory Syncytial
      Virus (RSV) bronchiolitis.

      HYPOTHESES

      In infants hospitalized with RSV bronchiolitis, azithromycin therapy (compared to placebo)
      will result in:

        1. Decreased concentrations of inflammatory mediators (IL-8 as primary outcome) in serum
           and nasal wash measured on day 8 after randomization.

        2. A smaller proportion of participants with recurrent (≥2) wheezing episodes during weeks
           3-52 following randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age: 1-18 months.

          2. Hospitalization for the first episode of RSV bronchiolitis:

               -  Confirmed RSV infection by positive nasal swab results (viral culture and/or
                  direct antigen detection) from the SLCH virology lab; AND

               -  At least two of the following symptoms/signs of bronchiolitis: respiratory rate
                  greater than 40 breaths/minute; cough; wheezing; audible rales, crackles, and/or
                  rhonchi; paradoxical chest movements (retractions).

          3. Duration of respiratory symptoms from initiation of symptoms to admission is 5 days or
             less. Time of admission will define by the time the child was seen in the ED for the
             visit that led to hospitalization.

          4. Randomization can be performed within 48 hours from time of admission (defined by time
             of first set of vital signs obtained on the floor).

          5. Willingness to provide informed consent by the child's parent or guardian

             -

        Exclusion Criteria:

          1. Prematurity (gestational age < 36 weeks).

          2. Presence or history of other significant disease (CNS, lung, cardiac, renal, GI,
             hepatic disease, hematologic, endocrine or immune disease). Children with atopic
             dermatitis will not be excluded from the study.

          3. Clinically significant gastroesophageal reflux currently treated with a daily
             anti-reflux medication (anti- H2 or PPI).

          4. The child has significant developmental delay/failure to thrive, defined as weight <
             3% for age and gender.

          5. History of previous (before the current episode) wheeze or previous treatment with
             albuterol.

          6. Treatment (past of present) with corticosteroid (systemic or inhaled) and/or
             montelukast.

          7. Treatment with any antibiotics in the past 2 weeks.

          8. Treatment with Macrolide antibiotic (Azithromycin, clarithromycin or erythromycin)
             with the past 4 weeks.

          9. Current treatment with any daily medication (other then albuterol, vitamins or
             nutritional supplements).

         10. Participation in another clinical trial.

         11. Evidence that the family may be unreliable or nonadherent, or may move from the
             clinical center area before trial completion.

         12. Contraindication of use of azithromycin or any other macrolide antibiotics.