search
Back to results

Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II (APW-RSV-II)

Primary Purpose

Respiratory Syncytial Virus, Bronchiolitis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oral azithromycin
Placebo
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Respiratory Syncytial Virus, Bronchiolitis

Eligibility Criteria

1 Month - 18 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age: 1-18 months.
  • Hospitalization for the first episode of RSV bronchiolitis.
  • Confirmed RSV infection by positive nasal swab results (PCR assay and/or direct antigen detection).
  • 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)28.
  • Duration of respiratory symptoms from onset of symptoms of the current illness to admission is 120 hours (5 days) or less.
  • Randomization can be performed within 168 hours (7 days) from onset of symptoms.
  • Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

  • Prematurity (gestational age < 36 weeks).
  • Presence or history of other significant disease (CNS, lung, cardiac, renal, GI, hepatic disease, hematologic, endocrine or immune disease). Children with atopic dermatitis and/or food allergy will not be excluded from the study.
  • Clinically significant gastroesophageal reflux currently treated with a daily anti-reflux medication (anti- H2 or PPI).
  • The child has significant developmental delay/failure to thrive, defined as weight < 3% for age and gender.
  • History of previous (before the current episode) wheeze or previous (before the current episode) treatment with albuterol.
  • History of previous treatment with corticosteroid (systemic or inhaled) for respiratory issues.
  • Treatment (past or present) with montelukast.
  • Treatment with any macrolide antibiotic (azithromycin, clarithromycin or erythromycin) over the past 4 weeks or current treatment with any macrolide antibiotic. Current or prior treatment with non-macrolide antibiotic is not an exclusion criterion.
  • Chronic treatment with any daily medication other than vitamins or nutritional supplements. Although routine vitamin D supplement (400 IU per day) is not an exclusion criterion, high dose vitamin D supplements are not allowed.
  • Participation in another clinical trial.
  • Participant requires invasive mechanical ventilation due to RSV bronchiolitis.
  • Evidence that the family may be unreliable or non-adherent, or has definitive plans to move from the clinical center area before trial completion.
  • Contraindication of use of azithromycin or any other macrolide antibiotics such as history of allergic reaction (or other adverse reaction) to these antibiotics.
  • Diagnosis of asthma.
  • Treatment with other medication that may cause QT interval prolongation.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Oral azithromycin

Placebo

Arm Description

Oral Azithromycin

Oral Placebo

Outcomes

Primary Outcome Measures

Number of Participants Who Experienced the Occurrence of a Third Episode of Post-RSV Wheezing (Recurrent Wheeze)
Episodes of wheezing were captured at each of the study telephone interviews and clinic visits using the question, "Has your child's chest sounded wheezy or whistling (with and without a cold)?". A new wheezing episode was defined if at least 7 days without wheezing had been reported since the previous episode.

Secondary Outcome Measures

Number of Participants Who Had Physician Asthma Diagnosis
Physician asthma diagnosis were captured at each of the study telephone interviews and clinic visits using the question, "Has the doctor told you that your child has asthma?".
Annualized Number of Days With Respiratory Symptoms (Wheezing, Cough, or Shortness of Breath)
The number of days with respiratory symptoms were captured during clinic visits and by telephone interviews every other month using two questions, "Does your child have coughing, wheezing, shortness of breath or chest tightness during the daytime?", "If yes, estimate the number of days". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Annualized Number of Days With Albuterol Use
The number of days with albuterol use were captured during clinic visits and by telephone interviews every other month using two questions, "Has your child taken Albuterol (also known as Ventolin, Pro-air, Proventil)?" and "please estimate # of days your child had albuterol treatments since the last visit". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Annualized Number of Oral Corticosteroid Courses
The number of oral corticosteroid courses were captured during clinic visits and by telephone interviews every other month using two questions, "Has your child taken Oral steroids (Prednisone, Prednisolone, Orapred, Dexamethasone)?" and "how many separate courses of steroids has your child had since the last visit?". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Annualized Number of Antibiotic Courses
The number of antibiotic courses were captured during clinic visits and by telephone interviews every other month using two questions, "Has your child taken any antibiotics?" and "How many separate prescriptions has your child taken of an antibiotic(s)?". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Number of Participants Who Experienced Serious Adverse Events
Serious Adverse Event were captured during clinic visits and by telephone interviews every other month using designed SAE form.

Full Information

First Posted
September 18, 2016
Last Updated
June 6, 2022
Sponsor
Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT02911935
Brief Title
Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II
Acronym
APW-RSV-II
Official Title
Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
April 2021 (Actual)
Study Completion Date
April 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main objective of the APW-RSV II clinical trial is to evaluate if the addition of azithromycin to routine bronchiolitis care, among infants hospitalized with RSV bronchiolitis, reduces the occurrence of recurrent wheeze during the preschool years.
Detailed Description
The APW-RSV II clinical trial is a double blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy 188 participants, ages 1-18 months, who are hospitalized due to RSV bronchiolitis. The study includes active treatment phase with azithromycin or placebo for 2 weeks, and an observational phase for up to 48 months. The main objective of the APW-RSV II clinical trial is to evaluate if the addition of azithromycin to routine bronchiolitis care, among infants hospitalized with RSV bronchiolitis, reduces the occurrence of recurrent wheeze (RW) during the preschool years. Study participants will be enrolled during 3 consecutive RSV seasons beginning in Fall 2016. Study participants will be randomized to receive PO azithromycin 10 mg/kg/day for 7 days followed by 5mg/kg/day for additional 7 days, or matched placebo. The primary clinical outcome is the time to the occurrence of a third episode of wheezing. The duration of follow up is 18-48 months, which is determined based on the year in which the participants is recruited: first year recruits will be followed for up to 48 months, while the 3rd year recruits will be followed for at least 18 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Virus, Bronchiolitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral azithromycin
Arm Type
Active Comparator
Arm Description
Oral Azithromycin
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral Placebo
Intervention Type
Drug
Intervention Name(s)
Oral azithromycin
Other Intervention Name(s)
Azithromycin suspension
Intervention Description
Oral azithromycin 10mg/kg/day for 7 days; then oral azithromycin 5mg/kg/day for 7 additional days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo suspension
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced the Occurrence of a Third Episode of Post-RSV Wheezing (Recurrent Wheeze)
Description
Episodes of wheezing were captured at each of the study telephone interviews and clinic visits using the question, "Has your child's chest sounded wheezy or whistling (with and without a cold)?". A new wheezing episode was defined if at least 7 days without wheezing had been reported since the previous episode.
Time Frame
Follow up duration of 18-48 months
Secondary Outcome Measure Information:
Title
Number of Participants Who Had Physician Asthma Diagnosis
Description
Physician asthma diagnosis were captured at each of the study telephone interviews and clinic visits using the question, "Has the doctor told you that your child has asthma?".
Time Frame
Follow up duration of 18-48 months
Title
Annualized Number of Days With Respiratory Symptoms (Wheezing, Cough, or Shortness of Breath)
Description
The number of days with respiratory symptoms were captured during clinic visits and by telephone interviews every other month using two questions, "Does your child have coughing, wheezing, shortness of breath or chest tightness during the daytime?", "If yes, estimate the number of days". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Time Frame
Follow up duration of 18-48 months
Title
Annualized Number of Days With Albuterol Use
Description
The number of days with albuterol use were captured during clinic visits and by telephone interviews every other month using two questions, "Has your child taken Albuterol (also known as Ventolin, Pro-air, Proventil)?" and "please estimate # of days your child had albuterol treatments since the last visit". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Time Frame
Follow up duration of 18-48 months
Title
Annualized Number of Oral Corticosteroid Courses
Description
The number of oral corticosteroid courses were captured during clinic visits and by telephone interviews every other month using two questions, "Has your child taken Oral steroids (Prednisone, Prednisolone, Orapred, Dexamethasone)?" and "how many separate courses of steroids has your child had since the last visit?". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Time Frame
Follow up duration of 18-48 months
Title
Annualized Number of Antibiotic Courses
Description
The number of antibiotic courses were captured during clinic visits and by telephone interviews every other month using two questions, "Has your child taken any antibiotics?" and "How many separate prescriptions has your child taken of an antibiotic(s)?". We used a negative binomial regression analysis with an offset term to adjust for duration of follow-up to get the annualized rate estimate.
Time Frame
Follow up duration of 18-48 months
Title
Number of Participants Who Experienced Serious Adverse Events
Description
Serious Adverse Event were captured during clinic visits and by telephone interviews every other month using designed SAE form.
Time Frame
Follow up duration of 18-48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
18 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 1-18 months. Hospitalization for the first episode of RSV bronchiolitis. Confirmed RSV infection by positive nasal swab results (PCR assay and/or direct antigen detection). 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)28. Duration of respiratory symptoms from onset of symptoms of the current illness to admission is 120 hours (5 days) or less. Randomization can be performed within 168 hours (7 days) from onset of symptoms. Willingness to provide informed consent by the child's parent or guardian. Exclusion Criteria: Prematurity (gestational age < 36 weeks). Presence or history of other significant disease (CNS, lung, cardiac, renal, GI, hepatic disease, hematologic, endocrine or immune disease). Children with atopic dermatitis and/or food allergy will not be excluded from the study. Clinically significant gastroesophageal reflux currently treated with a daily anti-reflux medication (anti- H2 or PPI). The child has significant developmental delay/failure to thrive, defined as weight < 3% for age and gender. History of previous (before the current episode) wheeze or previous (before the current episode) treatment with albuterol. History of previous treatment with corticosteroid (systemic or inhaled) for respiratory issues. Treatment (past or present) with montelukast. Treatment with any macrolide antibiotic (azithromycin, clarithromycin or erythromycin) over the past 4 weeks or current treatment with any macrolide antibiotic. Current or prior treatment with non-macrolide antibiotic is not an exclusion criterion. Chronic treatment with any daily medication other than vitamins or nutritional supplements. Although routine vitamin D supplement (400 IU per day) is not an exclusion criterion, high dose vitamin D supplements are not allowed. Participation in another clinical trial. Participant requires invasive mechanical ventilation due to RSV bronchiolitis. Evidence that the family may be unreliable or non-adherent, or has definitive plans to move from the clinical center area before trial completion. Contraindication of use of azithromycin or any other macrolide antibiotics such as history of allergic reaction (or other adverse reaction) to these antibiotics. Diagnosis of asthma. Treatment with other medication that may cause QT interval prolongation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Avraham Beigelman, MD, MSCI
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to study documents, including the study protocol with any amendments and blank case report forms. Upon reasonable request, these data will be provided by Dr. Charles Goss, the study statistician. email: cwgoss@wustl.edu
IPD Sharing Time Frame
A month after publication
IPD Sharing Access Criteria
See above

Learn more about this trial

Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II

We'll reach out to this number within 24 hrs