Macrolides to Prevent Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease

May 9, 2013 updated by: Jerry A. Krishnan, Johns Hopkins University
The purpose of this study is to determine whether macrolide therapy is effective in treating patients hospitalized with asthma exacerbations or chronic obstructive pulmonary disease (COPD)exacerbations. We hypothesize that compared to placebo, maintenance therapy with macrolides, when added to usual care, a) improves respiratory symptoms, b) improves quality of life, c) reduces airway inflammation, d) reduces airflow obstruction, and e) decreases the rate of re-exacerbations.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Asthma and chronic obstructive pulmonary disease (COPD) are the two most common obstructive lung diseases. Chronic airway inflammation and episodic worsening of respiratory symptoms and airflow obstruction (exacerbations) occur in asthma and COPD. Despite major advances in the development of therapies for these respiratory disorders, asthma and COPD exacerbations are common and result in substantial morbidity and mortality. Moreover, patients hospitalized for asthma or COPD exacerbations are at high risk for near fatal and fatal re-exacerbations after discharge home. These observations highlight the need for novel therapies to prevent asthma and COPD exacerbations. The role of macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin) in treating bacterial infections is well established. Recent pre-clinical evidence also suggests that macrolides may posses distinct anti-inflammatory properties and even anti-viral properties. These exciting observations have led to research evaluating the use of maintenance therapy with macrolides in patients with asthma and COPD. Small studies in clinically stable asthma or COPD suggest that maintenance macrolide therapy (e.g., use for 6 weeks), when added to usual care, may attenuate airway inflammation, reduce respiratory symptoms, and improve lung function. However, there are no studies that have evaluated the potential benefits of initiating maintenance macrolide therapy during asthma or COPD exacerbations. We hypothesize that initiating maintenance macrolide therapy in hospitalized patients with asthma or COPD exacerbations will, when added to usual medical care, accelerate the improvement in airflow obstruction, respiratory symptoms, and quality of life and reduce the risk of re-exacerbations after discharge home. The objective of this pilot study is to evaluate the feasibility of the study protocol (recruitment, retention, and adherence to study procedures and medications), as well as collect preliminary data about the proportion of exacerbations due to bacterial or viral infections and estimate potential effect sizes for clinically important outcomes (respiratory symptoms, quality of life, airflow obstruction, airway inflammation, and rate of re-exacerbations). To achieve these objectives, we propose a 48 week randomized, double-blind, placebo-controlled crossover clinical trial (24 weeks azithromycin, 24 weeks placebo) in adults hospitalized for asthma or COPD exacerbations to the Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center.

Study Type

Interventional

Enrollment

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Physician-diagnosis of asthma, COPD exacerbation, or undifferentiated asthma/COPD exacerbation
  • Admitted to the inpatient medical service at Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center
  • Evidence of airflow obstruction on spirometry (FEV1/FVC<70%)
  • Age 18 years or older

Exclusion Criteria:

  • History of allergy or other contraindication to macrolides (azithromycin, erythromycin, clarithromycin)
  • Treatment with any macrolide in the 4 weeks prior to study entry
  • Elevated AST or ALT (2 or more times the upper limit of normal) on current admission
  • Elevated alkaline phosphatase (>1.25 times the upper limit of normal) on current admission
  • Elevated total serum bilirubin (more than upper limit of normal) on current admission
  • Previous participation in this study
  • Patients prescribed digoxin (azithromycin may increase digoxin levels)
  • Patients prescribed warfarin (azithromycin may increase INR in patients on warfarin)
  • Patients prescribed pimozide (azithromycin may increase risk of arrhythmias)
  • Patient unable to provide consent (e.g., language difficulty or history of dementia)
  • Patient to be discharged to a location other than home (e.g., other hospital, long-term care facility)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The effect of azithromycin on the rate of exacerbations for asthma or COPD exacerbations after hospital discharge

Secondary Outcome Measures

Outcome Measure
changes in airflow obstruction (FEV1% predicted)
serum biomarkers of airway inflammation (IL-1beta, IL-5, IL-6, IL-8, IL-10, RANTES, IFN-gamma, TNF-alpha, and hs-CRP)
respiratory markers of inflammation (EBC measurements - pH)
symptom/quality of life measures

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Principal Investigator: Jerry A Krishnan, MD, PhD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

July 1, 2006

Study Completion (Actual)

July 1, 2006

Study Registration Dates

First Submitted

September 15, 2005

First Submitted That Met QC Criteria

September 15, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Estimate)

May 13, 2013

Last Update Submitted That Met QC Criteria

May 9, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-02-17-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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