Azithromycin for Children Hospitalized With Asthma

NCT ID: NCT02003911

Last Updated: 2020-08-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2018-06-01

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Azithromycin suspension

Azithromycin suspension at 10mg/kg/dose (max 500mg)

Once daily for 3 days

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Azithromycin suspension (200mg/5mL)

Placebo suspension

Same volume as active drug

Once daily for 3 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Azithromycin

Azithromycin suspension (200mg/5mL)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lindsey C Douglas, MD

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Katherine O'Connor, MD

Role: STUDY_DIRECTOR

Montefiore Medical Center

Diana S. Lee, MD

Role: STUDY_DIRECTOR

Montefiore Medical Center

Alyssa H Silver, MD

Role: STUDY_DIRECTOR

Montefiore Medical Center

Locations

The Children's Hospital at Montefiore

The Bronx, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

12-05-187

Identifier Type: -

Identifier Source: org_study_id