Clinical trial NCT01486758: Azithromycin to Prevent Wheezing Following Severe Respiratory Syncytial Virus (RSV) Bronchiolitis
Official title: Pilot Study: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: RSV Bronchiolitis
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2011-12-06
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: IL-8 Concentrations
timeFrame: Day 8
measure: Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes
timeFrame: 3-52 weeks following randomization
Secondary outcomes:
measure: Concentrations of IL-8 in Nasal Lavage on Day 15
timeFrame: Day 15
measure: Rates of Drug Related GI Side Effects.
timeFrame: One month from randomization
measure: Likelihood to Develop 3 or More Wheezing Episodes
timeFrame: Week 3-52
measure: Respiratory Symptoms Following RSV Bronchiolitis
timeFrame: 3-52 weeks following randomization
measure: Number of Children Who Were Prescribed Inhaled Corticosteroids
timeFrame: 3-52 weeks following randomization
measure: Proportion of Participants With a Physician Diagnosis of Asthma
timeFrame: Week 3-52
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Avraham Beigelman, MD, MSCI
role: PRINCIPAL_INVESTIGATOR
References: