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

• ClinicalTrials.gov Identifier: NCT01486758
• Recruitment Status: Completed
• First Posted: December 6, 2011
• Results First Posted: June 14, 2017
• Last Update Posted: June 14, 2017
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Avraham Beigelman, Washington University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
RSV Bronchiolitis	Drug: Azithromycin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pilot Study: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis
• Study Start Date: December 2011
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
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.
Placebo Comparator: Placebo; Oral Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. IL-8 Concentrations [ Time Frame: 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.
2. Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 18 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Missouri

Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

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

More Information

• Responsible Party: Avraham Beigelman, Assistant Professor of Pediatrics, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01486758
• Other Study ID Numbers: 201107151; ICTS, Washington University ( Other Grant/Funding Number: CTSA402 )
• First Posted: December 6, 2011
• Results First Posted: June 14, 2017
• Last Update Posted: June 14, 2017
• Last Verified: May 2017

Additional relevant MeSH terms:

Bronchiolitis; Respiratory Sounds; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Signs and Symptoms, Respiratory; Azithromycin; Anti-Bacterial Agents; Anti-Infective Agents