Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, Exacerbation, Macrolide
Brief summary
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease. Azithromycin, an antibiotic, may be beneficial at reducing the symptoms and severity of the disease. This study will analyze previously collected study data to evaluate the anti-inflammatory properties of azithromycin and determine how azithromycin affects the frequency and severity of COPD exacerbations.
Detailed description
COPD is a disease in which the lung airways are partly damaged and obstructed, making it difficult to breathe. The most common cause is cigarette smoking, but breathing in other types of lung irritants, including pollution, dust, and chemicals, over a long period of time may also contribute to COPD. It is the fourth leading cause of death in the United States. Symptoms include coughing, excess mucus production, shortness of breath, wheezing, and chest tightness. Some bacterial infections may worsen COPD exacerbations. Current studies are examining if the macrolide antibiotic azithromycin may be beneficial at reducing the frequency and/or severity of COPD exacerbations. Azithromycin also has anti-inflammatory properties that may reduce the severity of COPD exacerbations by inhibiting the matrix metalloprotease (MMP)-catalyzed breakdown of collagen and the subsequent generation of proline-glycine-proline (PGP), a substance produced in response to collagen breakdown. An increase in PGP levels may indicate an increase in inflammation, which can worsen COPD symptoms. NHLBI's COPD Network Macrolide study includes people with COPD who were randomly assigned to receive either azithromycin or placebo for 1 year. For this current study, researchers will examine the Macrolide participants' previously collected blood samples, sputum samples, and study data, including information on COPD exacerbations and azithromycin effects. The purpose of this study is to examine the anti-inflammatory properties of azithromycin in people with COPD.
Interventions
DRUGAzithromycin
250 mg daily
DRUGPlacebo
Daily
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Alabama at Birmingham
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participating in the COPD Network Macrolide study * Clinical diagnosis of at least moderate COPD * Cigarette consumption of 10 pack years or more
Exclusion criteria
* Diagnosis of asthma * Predicted life expectancy of less than 3 years * History of hypersensitivity to macrolide antibiotics * Long-term kidney insufficiency * Long-term liver insufficiency * Prolonged QT interval * Use of medications that may prolong the QT interval
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin. | Baseline to 12 months | Nasopharyngeal swabs were obtained to determine if there is a reduction in PGP levels (including both PGP & Neutrophil-PGP) after chronic treatment with azithromycin. Unblinding of the parent trial revealed that there were 18 sputum samples from 13 placebo-treated participants and 14 sputum samples from 8 azithromycin-treated participants collected at months 1 through 12 of treatment (with sputum samples not being available, this greatly reduced the sample size). |
Countries
United States
Participant flow
Recruitment details
Protocol Open to Accrual: August 2007, Primary Completion Date: July 2011 and Study Completion Date: July 2012. Recruitment location: University of Alabama at Birmingham and the Mayo Clinic.
Pre-assignment details
This research was conducted as an ancillary study to a multicenter trial (NCT00325897) of the efficacy of azithromycin treatment for 1 year in preventing chronic obstructive pulmonary disease (COPD) exacerbations to test whether sputum levels of proline-glycine-proline (PGP) were altered by treatment or associated with exacerbation frequency.
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin-treated Participants in the COPD Network Macrolide Study who received azithromycin for 1 year.
Azithromycin: 250 mg daily | 23 |
| Placebo-treated Participants in the COPD Network Macrolide Study who received placebo for 1 year.
Placebo: Daily | 30 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Sputum & Blood Samples Not Available | 15 | 17 |
Baseline characteristics
| Characteristic | Azithromycin-treated | Total | Placebo-treated |
|---|---|---|---|
| Age, Continuous | 64.4 years | 67.6 years | 70.8 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 23 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 30 Participants | 18 Participants |
| Region of Enrollment United States | 23 Participants | 53 Participants | 30 Participants |
| Sex: Female, Male Female | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Male | 17 Participants | 37 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 13 |
| other Total, other adverse events | 0 / 8 | 0 / 13 |
| serious Total, serious adverse events | 0 / 8 | 0 / 13 |
Outcome results
Primary
Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin.
Nasopharyngeal swabs were obtained to determine if there is a reduction in PGP levels (including both PGP & Neutrophil-PGP) after chronic treatment with azithromycin. Unblinding of the parent trial revealed that there were 18 sputum samples from 13 placebo-treated participants and 14 sputum samples from 8 azithromycin-treated participants collected at months 1 through 12 of treatment (with sputum samples not being available, this greatly reduced the sample size).
Time frame: Baseline to 12 months
Population: Levels of PGP from sputum samples are compared between subjects on the macrolide antibiotic, azithromycin, and subjects on placebo and correlated with neutrophil counts and protease activity in sputum.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Azithromycin-treated | Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin. | 2.27 ng/mL |
| Placebo-treated | Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin. | 5.15 ng/mL |
p-value: 0.045t-test, 1 sided