Clinical trial NCT02003911: Azithromycin for Children Hospitalized With Asthma
Official title: A Double-Blind, Randomized, Placebo-Controlled Trial of Azithromycin in Children Hospitalized With Acute Asthma Exacerbations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma
Acute asthma exacerbation
Pediatric
Azithromycin
Macrolide
Length of Stay
Hospital Medicine
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2013-12-06
Enrollment: 159
Sex: ALL
Minimum age (years): 4
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Length of Stay
timeFrame: Admission time to discharge time (average LOS is 3 days)
Secondary outcomes:
measure: Readmission Rate
timeFrame: One month after discharge
measure: School Missed
timeFrame: One month after discharge
measure: Work Missed
timeFrame: One month after discharge
measure: Emergency Room Visits
timeFrame: One month after discharge
measure: Physician Office Visits
timeFrame: One month after discharge
measure: Recurrence of Asthma Symptoms
timeFrame: One month after discharge
measure: Steroid Courses
timeFrame: One month after discharge
Other outcomes:
measure: Routine Clinical Results and Symptoms
timeFrame: One week after discharge
Locations:
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Lindsey C Douglas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center
name: Katherine O'Connor, MD
role: STUDY_DIRECTOR
affiliation: Montefiore Medical Center
name: Diana S. Lee, MD
role: STUDY_DIRECTOR
affiliation: Montefiore Medical Center
name: Alyssa H Silver, MD
role: STUDY_DIRECTOR
References: