RSV Bronchiolitis
Conditions
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.
Interventions
DRUGAzithromycin
Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days.
DRUGPlacebo
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IL-8 Concentrations | 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. |
| Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes | 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
| Measure | Time frame | Description |
|---|---|---|
| Rates of Drug Related GI Side Effects. | One month from randomization | — |
| Likelihood to Develop 3 or More Wheezing Episodes | Week 3-52 | Likelihood to develop 3 or more wheezing episodes measured by a Kaplan-Meier survival analysis |
| Number of Children Who Were Prescribed Inhaled Corticosteroids | 3-52 weeks following randomization | — |
| Proportion of Participants With a Physician Diagnosis of Asthma | Week 3-52 | The proportion of participants with a physician diagnosis of asthma |
| Respiratory Symptoms Following RSV Bronchiolitis | 3-52 weeks following randomization | Number of days with respiratory symptoms (cough, wheeze, or shortness of breath) |
| Concentrations of IL-8 in Nasal Lavage on Day 15 | Day 15 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin Azithromycin: Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days. | 20 |
| Placebo Azithromycin: Oral azithromycin 10 mg/kg once daily for 7 days followed by 5mg/kg once daily for additional 7 days. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Azithromycin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 20 Participants | 40 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 13 Participants | 25 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 9 Participants | 14 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 20 | 7 / 19 |
| serious Total, serious adverse events | 1 / 20 | 2 / 19 |
Outcome results
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.
Time frame: Day 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | IL-8 Concentrations | 12,795 Pg/ml |
| Azithromycin | IL-8 Concentrations | 14,676 Pg/ml |
p-value: 0.6ANCOVA
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.
Time frame: 3-52 weeks following randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes | .50 Proportion of participants |
| Azithromycin | Proportion of Participants Who Experience Subsequent Recurrent (≥2) Wheezing Episodes | .39 Proportion of participants |
Secondary
Concentrations of IL-8 in Nasal Lavage on Day 15
Time frame: Day 15
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Concentrations of IL-8 in Nasal Lavage on Day 15 | 2,318 pg/ml |
| Azithromycin | Concentrations of IL-8 in Nasal Lavage on Day 15 | 865 pg/ml |
Secondary
Likelihood to Develop 3 or More Wheezing Episodes
Likelihood to develop 3 or more wheezing episodes measured by a Kaplan-Meier survival analysis
Time frame: Week 3-52
Population: A Kaplan-Meier survival analysis was conducted to compare the likelihood of developing a third episode of wheezing among participants who received azithromycin versus those who received placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Likelihood to Develop 3 or More Wheezing Episodes | 50 percentage of participants |
| Azithromycin | Likelihood to Develop 3 or More Wheezing Episodes | 22 percentage of participants |
p-value: 0.048Log Rank
Secondary
Number of Children Who Were Prescribed Inhaled Corticosteroids
Time frame: 3-52 weeks following randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Children Who Were Prescribed Inhaled Corticosteroids | 6 Number of participants |
| Azithromycin | Number of Children Who Were Prescribed Inhaled Corticosteroids | 1 Number of participants |
Secondary
Proportion of Participants With a Physician Diagnosis of Asthma
The proportion of participants with a physician diagnosis of asthma
Time frame: Week 3-52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With a Physician Diagnosis of Asthma | .25 Percentage of participants |
| Azithromycin | Proportion of Participants With a Physician Diagnosis of Asthma | .11 Percentage of participants |
Secondary
Rates of Drug Related GI Side Effects.
Time frame: One month from randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Rates of Drug Related GI Side Effects. | 8 Number of participants |
| Azithromycin | Rates of Drug Related GI Side Effects. | 7 Number of participants |
Secondary
Respiratory Symptoms Following RSV Bronchiolitis
Number of days with respiratory symptoms (cough, wheeze, or shortness of breath)
Time frame: 3-52 weeks following randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Respiratory Symptoms Following RSV Bronchiolitis | 70.1 Number of days | Standard Deviation 43.1 |
| Azithromycin | Respiratory Symptoms Following RSV Bronchiolitis | 36.7 Number of days | Standard Deviation 28 |