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

RSV Bronchiolitis Clinical Trial

— APW-RSV  

Official title:

Pilot Study: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01486758
• Other study ID #: 201107151
• Secondary ID: ICTS, Washington
• Status: Completed
• Phase: Phase 2
• First received: November 28, 2011
• Last updated: June 3, 2014
• Start date: December 2011
• Est. completion date: May 2014

Study information

• Verified date: April 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 18 Months

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchiolitis
• RSV Bronchiolitis

Intervention

Drug:
• Azithromycin
Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days.

Locations

Country	Name	City	State
United States	Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Concentrations of inflammatory mediators in nasal lavage and serum measured on day 8, 15 (nasal lavage only) from randomization.	Inflammatory mediators: IL-8, CCL-2, CCL-3, CCL-4, CCL-5, G-CSF, IL-2, IL-4, IL-5 , IL-10, IL-12, IL-13, INF-g, eotaxin.	8, 15 days	No
Secondary	Rates of drug related side effects.		One month from randomization	Yes
Secondary	Clinical severity of acute bronchiolitis	Length of hospitalization (hr), duration of supplemental oxygen (hr), duration of supplemental IV fluids (hr).	During the acute hospitalization: expected lenght of hospitalization is 3 days	No
Secondary	Respiratory Symptoms (and treatments) following RSV bronchiolitis	Proportion of children with one and 3 wheezing episode; time to 1st, 2nd and 3rd episodes of wheezing; Number of: a) wheezing episodes, b) days/nights with wheezing/cough, c) days with use of rescue albuterol, d) courses of oral corticosteroids and antibiotics, e) MD/ED visits and hospitalizations for respiratory symptoms, and f) days with parental absence from work and infant absence from day care, g) days/nights with respiratory symptoms.	3-52 weeks following randomization	No
Secondary	Asthma Dx	Proportion of children with physician diagnosis of asthma.; Proportion of children who were prescribed asthma controllers medications (inhales corticosteroids and/or montelukast) during 52 weeks post-randomization.	3-52 weeks following randomization	No
Secondary	Quality of life	Quality of life measured by Quality of Life questionnaire	52 weeks following randomization	No
Secondary	Atopy	Proportion of children with at least one positive specific IgE (SIgE) to inhalant or food allergens at the end of study visit. We will measure the concentrations of SIgE to the following allergens: cat, dog, mite, rat, cockroach, mold mix, tree mix, grass mix, weed mix, cow's milk, egg white and peanut using the ImunoCAP platform (Phadia).; Mean total IgE level and eosinophil count.	52 weeks following randomization	No