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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Avraham Beigelman, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01486758
First received: November 28, 2011
Last updated: April 8, 2013
Last verified: April 2013
History of Changes
  Purpose

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 Intervention Phase
RSV Bronchiolitis
 Drug: Azithromycin
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • IL-8 concentrations [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3-52 weeks following randomization ] [ Designated as safety issue: No ]
    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:
  • Concentrations of inflammatory mediators in nasal lavage and serum measured on day 8, 15 (nasal lavage only) from randomization. [ Time Frame: 8, 15 days ] [ Designated as safety issue: No ]
    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.

  • Rates of drug related side effects. [ Time Frame: One month from randomization ] [ Designated as safety issue: Yes ]
  • Clinical severity of acute bronchiolitis [ Time Frame: During the acute hospitalization: expected lenght of hospitalization is 3 days ] [ Designated as safety issue: No ]
    Length of hospitalization (hr), duration of supplemental oxygen (hr), duration of supplemental IV fluids (hr).

  • Respiratory Symptoms (and treatments) following RSV bronchiolitis [ Time Frame: 3-52 weeks following randomization ] [ Designated as safety issue: No ]
    1. Proportion of children with one and 3 wheezing episode; time to 1st, 2nd and 3rd episodes of wheezing
    2. 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.

  • Asthma Dx [ Time Frame: 3-52 weeks following randomization ] [ Designated as safety issue: No ]
    1. Proportion of children with physician diagnosis of asthma.
    2. Proportion of children who were prescribed asthma controllers medications (inhales corticosteroids and/or montelukast) during 52 weeks post-randomization.

  • Quality of life [ Time Frame: 52 weeks following randomization ] [ Designated as safety issue: No ]
    Quality of life measured by Quality of Life questionnaire

  • Atopy [ Time Frame: 52 weeks following randomization ] [ Designated as safety issue: No ]
    1. 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).
    2. Mean total IgE level and eosinophil count.


Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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 Drug: Azithromycin
Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days.

  Eligibility

Ages Eligible for Study:   1 Month to 18 Months
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01486758

Locations
United States, Missouri
Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Avraham Beigelman, Assistant Professor of Pediatrics, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01486758     History of Changes
Other Study ID Numbers: 201107151, ICTS, Washington University
Study First Received: November 28, 2011
Last Updated: April 8, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bronchiolitis
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
 Respiratory Tract Infections
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013