APW-RSV-II: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02911935
• Collaborator: (none)
• Enrollment: 200
• Location: 1
• Arms: 2
• Actual Duration (Months): 53
• Patients Per Site Per Month: 3.8

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus, Bronchiolitis	Drug: Oral azithromycin; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Apr 1, 2021
• Actual Study Completion Date: Apr 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oral azithromycin Oral Azithromycin	Drug: Oral azithromycin; Oral azithromycin 10mg/kg/day for 7 days; then oral azithromycin 5mg/kg/day for 7 additional days; Other Names: Azithromycin suspension
Placebo Comparator: Placebo Oral Placebo	Drug: Placebo; Placebo suspension

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced the Occurrence of a Third Episode of Post-RSV Wheezing (Recurrent Wheeze) [Follow up duration of 18-48 months]

   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

1. Number of Participants Who Had Physician Asthma Diagnosis [Follow up duration of 18-48 months]

   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?".

2. Annualized Number of Days With Respiratory Symptoms (Wheezing, Cough, or Shortness of Breath) [Follow up duration of 18-48 months]

   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.

3. Annualized Number of Days With Albuterol Use [Follow up duration of 18-48 months]

   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.

4. Annualized Number of Oral Corticosteroid Courses [Follow up duration of 18-48 months]

   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.

5. Annualized Number of Antibiotic Courses [Follow up duration of 18-48 months]

   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.

6. Number of Participants Who Experienced Serious Adverse Events [Follow up duration of 18-48 months]

   Serious Adverse Event were captured during clinic visits and by telephone interviews every other month using designed SAE form.

Eligibility Criteria

Criteria

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 21, 2020

More Information

Publications

None provided.

• Responsible Party: Avraham Beigelman, Associate Professor of Pediatrics, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02911935
• Other Study ID Numbers: 201603018
• First Posted: Sep 22, 2016
• Last Update Posted: Jun 7, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Bronchiolitis; Respiratory Sounds; Azithromycin

Study Results

Participant Flow

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants received Azithromycin 10 mg/kg/d orally for 7 days and 5 mg/kg/d orally for additional 7 days	Participants received Azithromycin placebo orally daily for 14 days
Period Title: Overall Study
STARTED	101	99
COMPLETED	96	92
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Azithromycin	Placebo	Total
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days	Total of all reporting groups
Overall Participants	101	99	200
Age (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	3.9	2.8	3.3
Sex: Female, Male (Count of Participants)
Female	47 46.5%	44 44.4%	91 45.5%
Male	54 53.5%	55 55.6%	109 54.5%
Race/Ethnicity, Customized (Count of Participants)
African American	19 18.8%	21 21.2%	40 20%
Caucasian	72 71.3%	72 72.7%	144 72%
More than one race	10 9.9%	5 5.1%	15 7.5%
Region of Enrollment (Count of Participants)
United States	101 100%	99 100%	200 100%
Birth weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	3.3 (0.5)	3.4 (0.5)	3.3 (0.5)
Birth by cesarean section (Count of Participants)
Count of Participants [Participants]	29 28.7%	28 28.3%	57 28.5%
Gestational age at birth (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	38.9 (1.2)	38.8 (1.2)	38.8 (1.2)
Maternal smoking during pregnancy (Count of Participants)
Count of Participants [Participants]	19 18.8%	13 13.1%	32 16%
History of breast feeding (Count of Participants)
Count of Participants [Participants]	75 74.3%	80 80.8%	155 77.5%
History of eczema (Count of Participants)
Count of Participants [Participants]	16 15.8%	13 13.1%	29 14.5%
Food allergy diagnosis (Count of Participants)
Count of Participants [Participants]	3 3%	5 5.1%	8 4%
Parental history of asthma (Count of Participants)
Count of Participants [Participants]	33 32.7%	39 39.4%	72 36%
Parental history of other atopic diseases (Count of Participants)
Count of Participants [Participants]	60 59.4%	69 69.7%	129 64.5%
Pet exposure (Count of Participants)
Count of Participants [Participants]	59 58.4%	71 71.7%	130 65%
Tobacco smoke exposure (Count of Participants)
Count of Participants [Participants]	40 39.6%	26 26.3%	66 33%
Duration of hospital stay (hours) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [hours]	51	56	52
Duration of oxygen requirement, if required (hours) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [hours]	46	48	47
Lowest oxygen saturation on room air (percentage of oxygen saturation) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of oxygen saturation]	90.6 (4.4)	90.7 (5.2)	90.7 (4.8)
Need for BiPAP ventilation (Count of Participants)
Count of Participants [Participants]	8 7.9%	5 5.1%	13 6.5%
Bronchiolitis severity score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	5.3 (1.8)	5.2 (1.8)	5.2 (1.8)
Other nonstudy antibiotic (nonmacrolide) use (Count of Participants)
Count of Participants [Participants]	30 29.7%	28 28.3%	58 29%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

A total of 188 participants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit were included in the final primary outcome analysis.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	96	92
Count of Participants [Participants]	45 44.6%	33 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments	The primary analysis tested the statistical null hypothesis of equal recurrent wheeze rates between the azithromycin and placebo groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	unadjusted P-value. The threshold for statistical significance was p = 0.05
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95%; 0.95 to 2.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments	p-value is adjusted for race, parental history of asthma, ever exposed to smoke and ever exposed to pets. The threshold for statistical significance was p = 0.05
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.92 to 2.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

A total of 188 participants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit were included in the analysis.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	96	92
Count of Participants [Participants]	15 14.9%	8 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments	Unadjusted. The threshold for statistical significance was p = 0.05
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.95
	Confidence Interval	(2-Sided) 95%; 0.83 to 4.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

A total of 188 participants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit were included in this analysis.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	96	92
Mean (95% Confidence Interval) [days per year]	26.2	22.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments	Unadjusted. The threshold for statistical significance was p = 0.05
	Method	Negative Binomial Regression Analysis
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

A total of 188 participants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit were included in this analysis.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	96	92
Mean (95% Confidence Interval) [days per year]	4	3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	Unadjusted. The threshold for statistical significance was p = 0.05
	Method	Negative Binomial Regression Analysis
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.6 to 2.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

A total of 188 participants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit were included in this analysis.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	96	92
Mean (95% Confidence Interval) [courses per year]	0.23	0.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	unadjusted P-value. The threshold for statistical significance was p = 0.05
	Method	Negative Binomial Regression Analysis
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 0.70 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

A total of 188 participants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit were included in this analysis.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	96	92
Mean (95% Confidence Interval) [courses per year]	1.2	1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments	Unadjusted. The threshold for statistical significance was p = 0.05
	Method	Negative Binomial Regression Analysis
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days	Participants orally received Azithromycin placebo daily for 14 days
Measure Participants	101	99
Count of Participants [Participants]	15 14.9%	16 16.2%

Adverse Events

Time Frame	Follow up duration of 18-48 months
Arm/Group Title	Azithromycin		Placebo
Arm/Group Description	Participants orally received azithromycin 10mg/kg/day for 7 days; then oral azithromycin 5mg/kg/day for 7 additional days		Participants orally received placebo daily for 14 days.
All Cause Mortality
	Azithromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		0/99 (0%)
Serious Adverse Events
	Azithromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/101 (14.9%)		16/99 (16.2%)
Gastrointestinal disorders
Accidental drug ingestion	0/101 (0%)	0	1/99 (1%)	1
Acute appendicitis	1/101 (1%)	1	0/99 (0%)	0
Hospitalized with bloody diarrhea	0/101 (0%)	0	1/99 (1%)	1
General disorders
ED visit for gastroenteritis	0/101 (0%)	0	1/99 (1%)	1
Scheduled surgery for bilateral myringotomy with tube insertion and bilateral Adenotonsillectomy	0/101 (0%)	0	1/99 (1%)	1
Hospitalized for dehydration	0/101 (0%)	0	1/99 (1%)	1
Hospitalized for planned right open pyeloplasty and observation	1/101 (1%)	1	0/99 (0%)	0
Infections and infestations
High Fever	0/101 (0%)	0	2/99 (2%)	2
Preseptal Cellulitis	1/101 (1%)	1	0/99 (0%)	0
Hospitalized for a UTI and fever	0/101 (0%)	0	1/99 (1%)	1
Musculoskeletal and connective tissue disorders
Hospitalization for bone fracutre	0/101 (0%)	0	1/99 (1%)	1
Hospitalization with hematoma	1/101 (1%)	1	0/99 (0%)	0
Nervous system disorders
Hospitalized for observation and video EEG	0/101 (0%)	0	1/99 (1%)	1
Hospitalized with questionable seizurelike activity	0/101 (0%)	0	1/99 (1%)	1
Respiratory, thoracic and mediastinal disorders
Choking	0/101 (0%)	0	1/99 (1%)	1
Hospitalization for respiratory distress	0/101 (0%)	0	1/99 (1%)	1
Hospitalization for wheezing	4/101 (4%)	5	1/99 (1%)	2
Respiratory failure/distress	1/101 (1%)	1	0/99 (0%)	0
Transferred to PICU during respiratory infection	1/101 (1%)	1	3/99 (3%)	3
Hospitalized after bronchoscopy	1/101 (1%)	1	0/99 (0%)	0
Hospitalized for observation following bronchoscopy, BAL and EGD with biopsies	0/101 (0%)	0	1/99 (1%)	1
Hospitalized with respiratory infection	6/101 (5.9%)	6	3/99 (3%)	4
Hospitalized with pneumonia	1/101 (1%)	2	0/99 (0%)	0
Hospitalized for asthma exacerbation	0/101 (0%)	0	1/99 (1%)	3
Other (Not Including Serious) Adverse Events
	Azithromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/101 (72.3%)		72/99 (72.7%)
Blood and lymphatic system disorders
Abnormal Neutrophil Count	1/101 (1%)	1	1/99 (1%)	1
Abnormal platelet count	4/101 (4%)	4	1/99 (1%)	1
Decreased Neutrophil count	1/101 (1%)	1	0/99 (0%)	0
Eye disorders
Blocked tear duct	1/101 (1%)	1	0/99 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/101 (2%)	2	5/99 (5.1%)	5
GERD	1/101 (1%)	1	1/99 (1%)	1
Loose stool	3/101 (3%)	3	2/99 (2%)	2
Constipation	0/101 (0%)	0	3/99 (3%)	3
Diarrhea	30/101 (29.7%)	31	21/99 (21.2%)	21
Vomiting	10/101 (9.9%)	10	7/99 (7.1%)	7
General disorders
Blood in urine	1/101 (1%)	1	0/99 (0%)	0
Pneumonia	0/101 (0%)	0	1/99 (1%)	1
Infections and infestations
Acute Otitis Media	0/101 (0%)	0	1/99 (1%)	1
Skin infection	0/101 (0%)	0	1/99 (1%)	1
Ear infection	14/101 (13.9%)	14	14/99 (14.1%)	16
Fever	0/101 (0%)	0	1/99 (1%)	1
Pink eye	1/101 (1%)	1	0/99 (0%)	0
Strep infection	0/101 (0%)	0	1/99 (1%)	1
Nervous system disorders
Fussy	0/101 (0%)	0	1/99 (1%)	1
Sleep myoclonus	1/101 (1%)	1	0/99 (0%)	0
Respiratory, thoracic and mediastinal disorders
Wheezing	6/101 (5.9%)	6	5/99 (5.1%)	5
Severe obstructive sleep apnea	0/101 (0%)	0	1/99 (1%)	1
Upper respiratory infection	33/101 (32.7%)	33	22/99 (22.2%)	23
Skin and subcutaneous tissue disorders
Rash	8/101 (7.9%)	9	6/99 (6.1%)	7

Limitations/Caveats

Our ultimate goal was to examine an asthma prevention strategy. However, the primary outcome was defined as recurrent wheeze during 2-4 years of follow-up. This was previously done in other studies in this field. The study primary outcome measure was wheeze assessed by the parents, which has a relatively low correlation with wheeze assessed by physicians. However, a systematic bias is unlikely as both groups were evaluated by the same method

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.