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Pulmonary Disease, Chronic ObstructiveNCT00325897

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

A study testing Macrolide Antibiotic (Azithromycin) in people with Pulmonary Disease, Chronic Obstructive, run by University of Minnesota at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
Macrolide Antibiotic (Azithromycin)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,142 participants
Where
10 sitesUnited States
Study dates
Mar 2006to Jul 2010
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinical diagnosis of at least moderate Chronic Obstructive Pulmonary Disease (COPD), as defined by the following Global Initiative for COPD (GOLD) criteria:
  • Post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio of less than 70%
  • 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:
  • Current, or history of, supplemental O2 use
Show all 12Show fewer
  • Received a course of systemic corticosteroids for respiratory problems within 1 year prior to study entry
  • Visited an emergency department for a COPD exacerbation within 1 year prior to study entry
  • 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)

Who cannot join

  • 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:
Show all 21Show fewer
  • Cisapride
  • Ergot derivatives
  • Pimozide
  • Disopyramide
  • Cyclosporin
  • Tacrolimus
  • Nelfinavir
  • Bromocriptine
  • Hexobarbital
  • Corrected QT interval (QTc) 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 decibel (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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites
  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Maryland Baltimore

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Denver City-County Health/Hospitals Dept.

    Denver, Colorado, 80262

  • Minnesota Veterans Research Inst.

    Minneapolis, Minnesota, 55440

  • Temple University

    Philadelphia, Pennsylvania, 19140

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of California at San Francisco

    San Francisco, California, 94143

  • Harbor-UCLA Research & Education Inst.

    Torrance, California, 90502

Other trials in United States

About this study

Official title: 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).

Read the 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.

Being tested
Macrolide Antibiotic (Azithromycin), Placebo
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Macrolide Antibiotic (Azithromycin)Drug

    Also called Zithromax, Zmax

    Azithromycin (daily capsule, 250 mg for 12 months)

  • PlaceboDrug

    Also called sugar pill

    Placebo taken on a daily basis

Study groups in NCT00325897
Study groupRoleWhat they receive
Azithromycin, 250 mgActive comparatorMacrolide Antibiotic (Azithromycin)
Receives: Drug: Macrolide Antibiotic (Azithromycin)
PlaceboPlacebo comparatorInactive
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time Until First Occurrence of Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

    Time until first occurrence of acute Chronic Obstructive Pulmonary Disease (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 "

    Measured: Measured monthly through 13 months

Secondary outcomes (6)
  1. Exacerbations/Patient Year

    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 "

    Measured: Measured monthly until 13 months

  2. Number of Emergency Department Visits as a Result of Acute Exacerbations

    Measured: Measured monthly for 12 months

  3. Number of Hospital Admissions as a Result of Acute Exacerbations

    Measured: Measured monthly for 12 months

  4. Change in Age-adjusted Hearing Threshold

    Assessed by audiometry for four sound frequencies (1000, 2000, 3000, 4000 Hz). The maximum was computed for each threshold in each ear for all frequencies, then the differences between visits were assessed.

    Measured: Baseline and 12 months

  5. Incidence of Macrolide-resistant Bacterial Colonization of the Nasopharynx or Sputum

    Cultures from 68% of the participants in the azithromycin group and 70% in the placebo group who were not colonized with selected respiratory pathogens at the time of enrollment but who became colonized during the course of the study were available for susceptibility testing for the incidence of macrolide-resistant bacterial colonization.

    Measured: Baseline

  6. Incidence of Macrolide-resistant Bacterial Colonization of the Nasopharynx or Sputum

    Cultures from some participants who were not colonized with selected respiratory pathogens at the time of enrollment but who became colonized during the course of the study were available for susceptibility testing for the incidence of macrolide-resistant bacterial colonization.

    Measured: During Course of Study (either month 3, 6, 9, or 12)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionJun 2010
  4. Study completionJul 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
1,142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00325897
Sponsor's protocol ID
0510M76766
Other IDs
U10HL074424-03
Status last verified
Oct 2019
First submitted
12 May 2006
Last updated
18 Nov 2019
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Camac ER, Voelker H, Criner GJ; COPD Clinical Research Network and the Canadian Institutes of Health Research. Impact of COPD exacerbations leading to hospitalization on general and disease-specific quality of life. Respir Med. 2021 Sep;186:106526. doi: 10.1016/j.rmed.2021.106526. Epub 2021 Jun 29.

    PubMed 34229290
  • Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Leung JM, Paul Man SF, Aaron SD, Reed RM, Sin DD; Canadian Respiratory Research Network (CRRN). Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD. Respir Res. 2018 Feb 14;19(1):30. doi: 10.1186/s12931-018-0733-z.

    PubMed 29444682
  • Brown KE, Sin DD, Voelker H, Connett JE, Niewoehner DE, Kunisaki KM; COPD Clinical Research Network. Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations. Respir Res. 2017 Oct 24;18(1):179. doi: 10.1186/s12931-017-0664-0.

    PubMed 29065885
  • Wetherbee EE, Niewoehner DE, Sisson JH, Lindberg SM, Connett JE, Kunisaki KM. Self-reported alcohol intake and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study. Int J Chron Obstruct Pulmon Dis. 2015 Jul 20;10:1363-70. doi: 10.2147/COPD.S86572. eCollection 2015.

    PubMed 26229455
  • Geiger-Brown J, Lindberg S, Krachman S, McEvoy CE, Criner GJ, Connett JE, Albert RK, Scharf SM. Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2015 Feb 20;10:389-97. doi: 10.2147/COPD.S75840. eCollection 2015.

    PubMed 25759571
  • Han MK, Tayob N, Murray S, Dransfield MT, Washko G, Scanlon PD, Criner GJ, Casaburi R, Connett J, Lazarus SC, Albert R, Woodruff P, Martinez FJ. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1503-8. doi: 10.1164/rccm.201402-0207OC.

    PubMed 24779680
  • Albert RK, Connett J, Curtis JL, Martinez FJ, Han MK, Lazarus SC, Woodruff PG. Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2012;7:767-77. doi: 10.2147/COPD.S33714. Epub 2012 Nov 23.

    PubMed 23226013
  • Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR; COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011 Aug 25;365(8):689-98. doi: 10.1056/NEJMoa1104623.

    PubMed 21864166
  • Kunisaki KM, Niewoehner DE. Antibiotic prophylaxis for chronic obstructive pulmonary disease: resurrecting an old idea. Am J Respir Crit Care Med. 2008 Dec 1;178(11):1098-9. doi: 10.1164/rccm.200808-1315ED. No abstract available.

    PubMed 19023036

Questions about this trial

What is this clinical trial studying?

A study testing Macrolide Antibiotic (Azithromycin) in people with Pulmonary Disease, Chronic Obstructive, run by University of Minnesota at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time Until First Occurrence of Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (time frame: Measured monthly through 13 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00325897, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.

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