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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

May 12, 2006
June 18, 2013
March 2006
June 2010   (final data collection date for primary outcome measure)
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 "
time until first occurrence of acute COPD exacerbation (measured over a 1-year treatment period)
Complete list of historical versions of study NCT00325897 on ClinicalTrials.gov Archive Site
  • 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 ]
  • number of occurrences of acute exacerbations
  • number of emergency department visits as a result of acute exacerbations
  • number of hospital admissions as a result of acute exacerbations
  • number of hospital days as a result of acute exacerbations
  • incidence of presumed macrolide-related side-effects
  • incidence of presumed macrolide-related side effects that require cessation of treatment
  • incidence of macrolide-resistant bacterial colonization of the nasopharynx or sputum
  • incidence of pneumonia or acute bronchitis
  • quality of life
  • cost-effectiveness (all measured over a 12-month period)
Not Provided
Not Provided
 
Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease
Effect of Chronic Macrolide Administration on the Frequency and Severity of COPD Exacerbations

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).

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Pulmonary Disease, Chronic Obstructive
  • Drug: Macrolide Antibiotic (Azithromycin)
    Azithromycin (daily capsule, 250 mg for 12 months)
    Other Names:
    • Zithromax
    • Zmax
  • Drug: Placebo
    Placebo taken on a daily basis
    Other Name: sugar pill
  • Active Comparator: Azithromycin, 250 mg
    Macrolide Antibiotic (Azithromycin)
    Intervention: Drug: Macrolide Antibiotic (Azithromycin)
  • Placebo Comparator: Placebo
    Inactive
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1142
July 2010
June 2010   (final data collection date for primary outcome measure)

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
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00325897
397, U10HL074424-03
Yes
University of Minnesota - Clinical and Translational Science Institute
University of Minnesota - Clinical and Translational Science Institute
National Heart, Lung, and Blood Institute (NHLBI)
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
University of Minnesota - Clinical and Translational Science Institute
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP