Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00325897
First received: May 12, 2006
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine if long-term administration of a macrolide antibiotic will reduce worsening of symptoms among individuals with chronic obstructive pulmonary disease (COPD).


Condition Intervention
Pulmonary Disease, Chronic Obstructive
Drug: Macrolide Antibiotic (Azithromycin)
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Effect of Chronic Macrolide Administration on the Frequency and Severity of COPD Exacerbations

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Time Until First Occurrence of Acute COPD (Chronic Obstructive Pulmonary Disease) Exacerbation [ Time Frame: Measured monthly through 13 months ] [ Designated as safety issue: No ]
    Time until first occurrence of acute COPD exacerbation. Acute exacerbations are defined as a "complex of respiratory symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnea, or chest tightness with a duration of at least three days requiring treatment with antibiotics and/or systemic steroids "


Secondary Outcome Measures:
  • Exacerbations/Patient-year [ Time Frame: Measured montly until 13 months ] [ Designated as safety issue: No ]
    Acute exacerbations are defined as a "complex of respiratory symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnea, or chest tightness with a duration of at least three days requiring treatment with antibiotics and/or systemic steroids "

  • Number of Emergency Department Visits as a Result of Acute Exacerbations [ Time Frame: Measured at 12-13 months ] [ Designated as safety issue: No ]
  • Number of Hospital Admissions as a Result of Acute Exacerbations [ Time Frame: Measured at 12-13 months ] [ Designated as safety issue: No ]
  • Incidence of Presumed Macrolide-related Side-effects [ Time Frame: Measured at 12-13 months ] [ Designated as safety issue: Yes ]
  • Incidence of Presumed Macrolide-related Side Effects That Require Cessation of Treatment [ Time Frame: Measured at 12 months ] [ Designated as safety issue: Yes ]
  • Incidence of Macrolide-resistant Bacterial Colonization of the Nasopharynx or Sputum [ Time Frame: Measured at 12-13 months ] [ Designated as safety issue: Yes ]
  • Incidence of Pneumonia or Acute Bronchitis [ Time Frame: Measured at 12-13 months ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: Measured at 12-13 months ] [ Designated as safety issue: No ]

Enrollment: 1142
Study Start Date: March 2006
Study Completion Date: July 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Azithromycin, 250 mg
Macrolide Antibiotic (Azithromycin)
Drug: Macrolide Antibiotic (Azithromycin)
Azithromycin (daily capsule, 250 mg for 12 months)
Other Names:
  • Zithromax
  • Zmax
Placebo Comparator: Placebo
Inactive
Drug: Placebo
Placebo taken on a daily basis
Other Name: sugar pill

Detailed Description:

BACKGROUND:

The prevalence, morbidity, mortality, and treatment cost of COPD are high and increasing. COPD is the sixth leading cause of death worldwide and is the only condition in the top 10 causes of death that has an increasing prevalence and mortality. The cost of health care for patients with COPD in the U.S. is approximately $6.5 billion per year; acute exacerbations account for between 31% and 68% of that cost. Macrolide antibiotics may reduce the frequency and/or severity of COPD exacerbations, as a result of their antibacterial properties and anti-inflammatory effects. Long-term administration of macrolide antibiotics in patients with a number of other pulmonary disorders has resulted in clinically important improvements. It is hypothesized that administration of a macrolide antibiotic (azithromycin) for 1 year, when added to usual care, will decrease the frequency and severity of COPD exacerbations. If this hypothesis is correct, the proposed treatment is also expected to reduce the mortality of COPD patients.

DESIGN NARRATIVE:

This is a prospective, randomized, double-blind, placebo-controlled study that will enroll 1130 patients with at least moderately severe COPD who, based on clinical indicators, have an increased likelihood of experiencing an acute exacerbation during the study period. Patients will be monitored monthly, including careful assessments of possible macrolide-related side effects. The exclusion criteria for this study will include a variety of conditions or medications that are known to adversely interact with macrolides. The primary endpoint of this study is time until the first acute COPD exacerbation. The secondary endpoints include macrolide-related side effects, the incidence of macrolide-resistant bacterial colonization, quality of life, and cost-effectiveness.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of at least moderate COPD, as defined by the following GOLD criteria:

    1. Post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio of less than 70%
    2. Post-bronchodilator FEV1 less than 80% predicted, with or without chronic symptoms
  • Cigarette consumption of 10 pack-years or more (may or may not be active smokers)
  • Meets one or more of the following four conditions:

    1. Current, or history of, supplemental O2 use
    2. Received a course of systemic corticosteroids for respiratory problems within 1 year prior to study entry
    3. Visited an emergency department for a COPD exacerbation within 1 year prior to study entry
    4. Hospitalized for a COPD exacerbation within 1 year prior to study entry
  • Willing to make return visits
  • Available by telephone for duration of study
  • Minimum of 4 weeks from the most recent acute exacerbation (have not received a course of systemic corticosteroids, an increased dose of chronically administered systemic corticosteroids, and/or antibiotics for an acute exacerbation for a minimum of 4 weeks from the time of study entry)

Exclusion Criteria:

  • Diagnosis of asthma
  • Diagnosis other than COPD that results in the patient being either medically unstable, or having a predicted life expectancy less than 3 years
  • Special patient groups (i.e., prisoners, pregnant women, or institutionalized patients)
  • Women who are at risk of becoming pregnant during the study (pre-menopausal) and who refuse to use acceptable birth control (i.e., hormone-based oral or barrier contraceptive) for the duration of the study
  • History of hypersensitivity to any macrolide antibiotic
  • Taking any of the following medications:

    1. Cisapride
    2. Ergot derivatives
    3. Pimozide
    4. Disopyramide
    5. Cyclosporin
    6. Tacrolimus
    7. Nelfinavir
    8. Bromocriptine
    9. Hexobarbital
  • QTc interval on electrocardiogram exceeding 440 ms
  • Taking rifabutin or rifampin
  • Chronic hepatic insufficiency
  • Chronic renal insufficiency
  • Diagnosis of bronchiectasis (defined as production of greater than one-half cup of purulent sputum/day)
  • If, for either ear, formal audiometric testing in a sound booth results in a pure tone average (i.e., the average of the thresholds for the 4 frequencies 1000, 2000, 3000, or 4000) exceeding 50 dB, or if the threshold at any one frequency exceeds 60 dB, then the participant will be counseled by the audiologist concerning hearing aids and/or referral to an otolaryngologist. In addition, the audiologist may discuss with the participant whether or not to continue in the study. Following the examination and counseling, the participant will also discuss whether or not to continue in the study with one of the study investigators. If it is found that a participant's pure tone average in the two ears differs by more than 15 dB, or if the difference in the two ears for any one frequency exceeds 20 dB, then the participant will not be eligible for randomization into the study unless cleared by an otolaryngologist
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00325897

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, California
University of California at San Francisco
San Francisco, California, United States, 94143
Harbor-UCLA Research & Education Inst.
Torrance, California, United States, 90502
United States, Colorado
Denver City-County Health/Hospitals Dept.
Denver, Colorado, United States, 80262
United States, Maryland
University of Maryland Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Minnesota Veterans Research Inst.
Minneapolis, Minnesota, United States, 55440
United States, Pennsylvania
Temple University
Philadelphia, Pennsylvania, United States, 19140
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Richard K. Albert, MD Denver City-County Health/Hospitals Department
Principal Investigator: William C. Bailey, MD University of Alabama at Birmingham
Principal Investigator: Richard Casaburi, MD, PhD Harbor-UCLA Research & Education Institute
Principal Investigator: John E. Connett, PhD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Gerard J. Criner, MD Temple University
Principal Investigator: Stephen C. Lazarus, MD University of California at San Francisco
Principal Investigator: Fernando J. Martinez, MD University of Michigan
Principal Investigator: Dennis E. Niewoehner, MD Minnesota Veterans Research Institute
Principal Investigator: John J. Reilly, MD Brigham and Women's Hospital
Principal Investigator: Steven M. Scharf, MD, PhD University of Maryland, Baltimore County
Principal Investigator: Frank Sciurba, MD University of Pittsburgh
  More Information

No publications provided by University of Minnesota - Clinical and Translational Science Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00325897     History of Changes
Other Study ID Numbers: 397, U10HL074424-03
Study First Received: May 12, 2006
Results First Received: August 18, 2011
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Anti-Bacterial Agents
Azithromycin
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on April 16, 2014