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

Pilot Study: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis

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.

Study Overview

• Status: Completed
• Conditions: RSV Bronchiolitis
• Intervention / Treatment: Drug: Placebo; Drug: Azithromycin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Oral Placebo	Drug: Placebo
Active Comparator: Azithromycin; Oral azithromycin	Drug: Azithromycin; Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-8 Concentrations	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.	Day 8
Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes	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.	3-52 weeks following randomization

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Avraham Beigelman, MD, MSCI, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 28, 2011
• First Submitted That Met QC Criteria: December 4, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis; Respiratory Sounds; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 201107151; ICTS, Washington University (Other Grant/Funding Number: CTSA402)