Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral azithromycin | Active Comparator | Oral Azithromycin |
|
| Placebo | Placebo Comparator | Oral Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral azithromycin | Drug | Oral azithromycin 10mg/kg/day for 7 days; then oral azithromycin 5mg/kg/day for 7 additional days |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Follow up duration of 18-48 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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?". | Follow up duration of 18-48 months |
| Annualized Number of Days With Respiratory Symptoms (Wheezing, Cough, or Shortness of Breath) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Avraham Beigelman, MD, MSCI | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38237675 | Derived | Beigelman A, Goss CW, Wang J, Srinivasan M, Boomer J, Zhou Y, Bram S, Casper TJ, Coverstone AM, Kanchongkittiphon W, Kuklinski C, Storch GA, Schechtman KB, Castro M, Bacharier LB. Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze. Ann Allergy Asthma Immunol. 2024 May;132(5):623-629. doi: 10.1016/j.anai.2024.01.001. Epub 2024 Jan 17. | |
| 37621674 |
Not provided
Not provided
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
A month after publication
See above
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Azithromycin | Participants received Azithromycin 10 mg/kg/d orally for 7 days and 5 mg/kg/d orally for additional 7 days |
| FG001 | Placebo | Participants received Azithromycin placebo orally daily for 14 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Azithromycin | Participants orally received Azithromycin 10 mg/kg/d for 7 days and 5 mg/kg/d for additional 7 days |
| BG001 | Placebo | Participants orally received Azithromycin placebo daily for 14 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Count of Participants | Participants | Follow up duration of 18-48 months |
|
Follow up duration of 18-48 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Azithromycin | Participants orally received azithromycin 10mg/kg/day for 7 days; then oral azithromycin 5mg/kg/day for 7 additional days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accidental drug ingestion | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Avraham Beigelman | Washington University School of Medicine. | 314-454-2694 | beigelmana@wustl.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 21, 2020 | Apr 18, 2022 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D001988 | Bronchiolitis |
| ID | Term |
|---|---|
| D001991 | Bronchitis |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo suspension |
|
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. |
| Follow up duration of 18-48 months |
| 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. | Follow up duration of 18-48 months |
| 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. | Follow up duration of 18-48 months |
| 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. | Follow up duration of 18-48 months |
| 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. | Follow up duration of 18-48 months |
| Derived |
| Beigelman A, Srinivasan M, Goss CW, Wang J, Zhou Y, True K, Ahrens E, Burgdorf D, Haslam MD, Boomer J, Bram S, Burnham CD, Casper TJ, Coverstone AM, Kanchongkittiphon W, Kuklinski C, Storch GA, Wallace MA, Yin-DeClue H, Castro M, Schechtman KB, Bacharier LB. Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis. NEJM Evid. 2022 Apr;1(4):10.1056/evidoa2100069. doi: 10.1056/evidoa2100069. Epub 2022 Feb 27. |
| BG002 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | One participant in Placebo arm refused to provide race/ethnicity information | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Birth weight | Mean | Standard Deviation | kg |
|
| Birth by cesarean section | Count of Participants | Participants |
|
| Gestational age at birth | Mean | Standard Deviation | weeks |
|
| Maternal smoking during pregnancy | Count of Participants | Participants |
|
| History of breast feeding | Count of Participants | Participants |
|
| History of eczema | Count of Participants | Participants |
|
| Food allergy diagnosis | Count of Participants | Participants |
|
| Parental history of asthma | Count of Participants | Participants |
|
| Parental history of other atopic diseases | Count of Participants | Participants |
|
| Pet exposure | Count of Participants | Participants |
|
| Tobacco smoke exposure | Count of Participants | Participants |
|
| Duration of hospital stay | Two patients with missing values were excluded from the analysis population. | Median | Inter-Quartile Range | hours |
|
| Duration of oxygen requirement, if required | The analysis population only included infants were supplemented with oxygen if they had oxygen saturation of less than 90% on room air. | Median | Inter-Quartile Range | hours |
|
| Lowest oxygen saturation on room air | Three patients with missing values were excluded from the analysis population. | Mean | Standard Deviation | percentage of oxygen saturation |
|
| Need for BiPAP ventilation | Two patients with missing values were excluded from the analysis population. | Count of Participants | Participants |
|
| Bronchiolitis severity score | Bronchiolitis severity score is the total score of 4 categories including Respiratory rate, Flaring or Retracting, Lowest Oxygen Saturation, and Wheezing. Each category is scored separately and then summed up to get the total score. The score for each category ranges from 0 to 3 with higher numbers indicating worse disease. The total score range from 0-12 with higher numbers indicating worse disease. | Mean | Standard Deviation | Scores on a scale |
|
| Other nonstudy antibiotic (nonmacrolide) use | Count of Participants | Participants |
|
| OG001 |
| Placebo |
Participants orally received Azithromycin placebo daily for 14 days |
|
|
|
| Secondary | 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?". | 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. | Posted | Count of Participants | Participants | Follow up duration of 18-48 months |
|
|
|
|
| Secondary | 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. | 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. | Posted | Mean | 95% Confidence Interval | days per year | Follow up duration of 18-48 months |
|
|
|
|
| Secondary | 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. | 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. | Posted | Mean | 95% Confidence Interval | days per year | Follow up duration of 18-48 months |
|
|
|
|
| Secondary | 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. | 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. | Posted | Mean | 95% Confidence Interval | courses per year | Follow up duration of 18-48 months |
|
|
|
|
| Secondary | 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. | 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. | Posted | Mean | 95% Confidence Interval | courses per year | Follow up duration of 18-48 months |
|
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | Follow up duration of 18-48 months |
|
|
|
| 0 |
| 101 |
| 15 |
| 101 |
| 73 |
| 101 |
| EG001 | Placebo | Participants orally received placebo daily for 14 days. | 0 | 99 | 16 | 99 | 72 | 99 |
| Acute appendicitis | Gastrointestinal disorders | Systematic Assessment |
|
| Choking | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| ED visit for gastroenteritis | General disorders | Systematic Assessment |
|
| High Fever | Infections and infestations | Systematic Assessment |
|
| Hospitalization for bone fracutre | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hospitalization for respiratory distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalization for wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalized for observation and video EEG | Nervous system disorders | Systematic Assessment |
|
| Preseptal Cellulitis | Infections and infestations | Systematic Assessment |
|
| Respiratory failure/distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Scheduled surgery for bilateral myringotomy with tube insertion and bilateral Adenotonsillectomy | General disorders | Systematic Assessment |
|
| Transferred to PICU during respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalization with hematoma | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hospitalized after bronchoscopy | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalized for a UTI and fever | Infections and infestations | Systematic Assessment |
|
| Hospitalized for dehydration | General disorders | Systematic Assessment |
|
| Hospitalized for observation following bronchoscopy, BAL and EGD with biopsies | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalized for planned right open pyeloplasty and observation | General disorders | Systematic Assessment |
|
| Hospitalized with respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalized with bloody diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Hospitalized with questionable seizurelike activity | Nervous system disorders | Systematic Assessment |
|
| Hospitalized with pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hospitalized for asthma exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Abnormal Neutrophil Count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Abnormal platelet count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Acute Otitis Media | Infections and infestations | Systematic Assessment |
|
| GERD | Gastrointestinal disorders | Systematic Assessment |
|
| Loose stool | Gastrointestinal disorders | Systematic Assessment |
|
| Skin infection | Infections and infestations | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Blocked tear duct | Eye disorders | Systematic Assessment |
|
| Blood in urine | General disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Decreased Neutrophil count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Ear infection | Infections and infestations | Systematic Assessment |
|
| Fever | Infections and infestations | Systematic Assessment |
|
| Fussy | Nervous system disorders | Systematic Assessment |
|
| Pink eye | Infections and infestations | Systematic Assessment |
|
| Pneumonia | General disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Severe obstructive sleep apnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sleep myoclonus | Nervous system disorders | Systematic Assessment |
|
| Strep infection | Infections and infestations | Systematic Assessment |
|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
Not provided
Not provided
| D012140 |
| Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| Organic Chemicals |
| More than one race |
|