Azithromycin for Children Hospitalized With Asthma

Study Overview
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Brief Summary
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Asthma is a chronic lung condition in children, and often requires hospitalization for acute exacerbations. Azithromycin has been used successfully in other chronic lung diseases, including cystic fibrosis. Despite limited clinical evidence, some pediatricians use azithromycin in children hospitalized with asthma, citing either treatment of atypical pathogens or its proposed anti-inflammatory properties. This study proposes a clinical trial to determine if azithromycin will shorten length of stay in children hospitalized with acute asthma exacerbations.

Detailed Description
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Asthma is a chronic lung condition that accounts for over 130,000 pediatric hospitalizations nationally at a cost of almost 1.4 billion dollars. Atypical pathogens have been implicated both in initiating asthma and triggering acute asthma exacerbations. Azithromycin, a macrolide antibiotic, is known to have antibacterial activity against atypical pathogens and gram positive bacteria. More recently, macrolides have been increasingly used and effective against gram negative bacteria and inflammation in the lungs of patients with chronic respiratory illnesses. This effect may be secondary to the immunomodulatory effects macrolides possess, in addition to their anti-bacterial effects. In long-term therapy with macrolides, patients with asthma have shown improved bronchiolar hyperreactivity, spirometry, symptoms, and quality of life. However, studies of short-term treatment in the acute setting and in children are limited. Some practitioners use azithromycin in the treatment of acute asthma, despite limited data. The investigators propose a double-blind, randomized, placebo-controlled trial of azithromycin in children aged 4-12 years with persistent asthma hospitalized with acute asthma exacerbations. Children will be enrolled within 12 hours of admission and will be randomized to receive three days of either azithromycin or placebo suspension (10mg/kg/dose, max of 500mg). The primary outcome measure will be length of stay (LOS). Secondary outcome measures will include: days of school/work missed, readmission rates, return to medical care rates, recurrence of symptoms, and steroid courses. In the future, patients may also be approached to enroll in the Mechanism Subset Study a separate pilot and feasibility study which will require two blood samples and two nasal aspirate samples and will test for atypical pathogens, interleukin-8 levels, and neutrophil/eosinophil counts. The average length of stay for patients in this age range with asthma in 2011 at our institution was 3.0 days. The investigators will enroll to achieve a power of 80%, with an alpha of 0.05, which will require 107 patients in each group to detect a 16 hour (0.67 day) difference in the primary outcome, LOS. This study hypothesizes that azithromycin treatment in children hospitalized with acute asthma will decrease LOS.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Trial of Azithromycin in Children Hospitalized With Acute Asthma Exacerbations

Conditions
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Asthma

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 4-12 years of age Admission diagnosis of asthma at the Children's Hospital at Montefiore History of persistent asthma (as defined by National Heart, Lung, and Blood Institute) Exclusion Criteria: Concurrent bacterial infection requiring antibiotics Antibiotics received within previous 2 weeks Contraindication to azithromycin (including allergy to macrolides) Chronic lung disease other than asthma (including bronchopulmonary dysplasia, cystic fibrosis, bronchiectasis) or home oxygen requirement Immunodeficiency (primary or acquired) Chronic systemic steroid use Invasive or non-invasive mechanical ventilation required acutely as result of current asthma admission Significant cardiac co-morbidity (including hemodynamically significant cardiac disease or arrhythmia) Liver disease (hepatitis) Pregnancy Seizure disorder, currently on anti-epileptic medication) Receiving albuterol every 4 hours (q4h) at the time of enrollment Previous enrollment in study

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin suspension<br>Azithromycin suspension at 10mg/kg/dose (max 500mg) Once daily for 3 days | Drug: Azithromycin<br>* Azithromycin suspension (200mg/5mL)<br>|
| Placebo Comparator: Placebo suspension<br>Same volume as active drug Once daily for 3 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Stay | Hospital length of stay | Admission time to discharge time (average LOS is 3 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Readmission Rate | Number of hospital readmissions for asthma at telephone follow-up phone calls at 1-week and 1-month interval after discharge | One month after discharge | 
| School Missed | Days of school missed by patient at telephone follow-up phone calls at 1-week and 1-month interval after discharge | One month after discharge | 
| Work Missed | Days of work missed by parent/guardian at telephone follow-up phone calls at 1-week and 1-month interval after discharge | One month after discharge | 
| Emergency Room Visits | Number of emergency room visits for asthma symptoms since discharge at telephone follow-up phone calls at 1-week and 1-month interval after discharge | One month after discharge | 
| Physician Office Visits | Number of physician office visits for asthma symptoms since discharge at telephone follow-up phone calls at 1-week and 1-month interval after discharge | One month after discharge | 
| Recurrence of Asthma Symptoms | Number of recurrences of asthma symptoms since discharge at telephone follow-up phone calls at 1-week and 1-month interval after discharge | One month after discharge | 
| Steroid Courses | Number of courses of oral steroids since discharge at telephone follow-up phone call 1-month after discharge | One month after discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Acute asthma exacerbation, Pediatric, Azithromycin, Macrolide, Length of Stay, Hospital Medicine