Azithromycin to Prevent Wheezing Following Severe Respiratory Syncytial Virus (RSV) Bronchiolitis

Phase 2

Completed

• Conditions: RSV Bronchiolitis
• Interventions: Drug: Azithromycin; Drug: Placebo

• Registration Number: NCT01486758
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-11-28
• Study Start: 2011-12
• Study First Submitted QC: 2011-12-04
• Study First Posted: 2011-12-06
• Primary Completion: 2014-04
• Study Completion: 2014-05
• Results First Submitted: 2016-04-12
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-15
• Last Update Submitted: 2017-05-15
• Results First Posted: 2017-06-14
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azithromycin	Azithromycin	Oral azithromycin
Placebo	Placebo	Oral Placebo

Primary Outcome Measures

Name	Time	Method
IL-8 Concentrations	Day 8	Biological outcome: The difference in IL-8 concentrations, measured in serum on day 8 after randomization, among infants treated with azithromycin and those treated with placebo.
Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes	3-52 weeks following randomization	Clinical outcome: The difference in the proportion of participants who experience subsequent recurrent (≥2) wheezing episodes among infants treated with azithromycin and those treated with placebo.

Secondary Outcome Measures

Name	Time	Method
Concentrations of IL-8 in Nasal Lavage on Day 15	Day 15
Respiratory Symptoms Following RSV Bronchiolitis	3-52 weeks following randomization	Number of days with respiratory symptoms (cough, wheeze, or shortness of breath)
Rates of Drug Related GI Side Effects.	One month from randomization
Likelihood to Develop 3 or More Wheezing Episodes	Week 3-52	Likelihood to develop 3 or more wheezing episodes measured by a Kaplan-Meier survival analysis
Number of Children Who Were Prescribed Inhaled Corticosteroids	3-52 weeks following randomization
Proportion of Participants With a Physician Diagnosis of Asthma	Week 3-52	The proportion of participants with a physician diagnosis of asthma

Trial Locations

Locations (1)

Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States