Azithromycin for Children Hospitalized With Asthma

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: Azithromycin

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.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • The Children's Hospital at Montefiore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Routine Clinical Results and Symptoms	Respiratory viral panel or rapid viral testing results (if obtained as part of medical care), chest x-ray results/lab results (if obtained as part of medical care), vital signs, medications received during admission, medication side effects (diarrhea, abdominal pain, vomiting, flatulence), transfer to intensive care unit, time of wean of beta-agonists (q3h and q4h), and asthma severity (PASS score) at time of enrollment.	One week after discharge

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Lindsey C Douglas, MD, Montefiore Medical Center; Study Director: Katherine O'Connor, MD, Montefiore Medical Center; Study Director: Diana S. Lee, MD, Montefiore Medical Center; Study Director: Alyssa H Silver, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: December 5, 2013
• First Posted (Estimate): December 6, 2013

Study Record Updates

• Last Update Posted (Actual): August 13, 2020
• Last Update Submitted That Met QC Criteria: August 11, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Asthma; Pediatric; Azithromycin; Macrolide; Length of Stay; Hospital Medicine; Acute asthma exacerbation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 12-05-187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes