Trial Outcomes & Findings for Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease (NCT NCT00325897)

Last Updated: 2019-11-18

Results Overview

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 "

Recruitment status

COMPLETED

Study phase

Target enrollment

1142 participants

Primary outcome timeframe

Measured monthly through 13 months

Results posted on

2019-11-18

Participant Flow

Participant milestones

Participant milestones
Measure	Azithromycin Azithromycin, 250 mg	Placebo Inactive sugar pill
Overall Study STARTED	570	572
Overall Study COMPLETED	558	559
Overall Study NOT COMPLETED	12	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Azithromycin Azithromycin, 250 mg	Placebo Inactive sugar pill
Overall Study Lost to Follow-up	12	13

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Azithromycin n=570 Participants Azithromycin, 250 mg	Placebo n=572 Participants Inactive sugar pill	Total n=1142 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	277 Participants n=5 Participants	261 Participants n=7 Participants	538 Participants n=5 Participants
Age, Categorical >=65 years	293 Participants n=5 Participants	311 Participants n=7 Participants	604 Participants n=5 Participants
Age, Continuous	64.8 years STANDARD_DEVIATION 8.7 • n=5 Participants	65.5 years STANDARD_DEVIATION 8.4 • n=7 Participants	65.1 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	234 Participants n=5 Participants	229 Participants n=7 Participants	463 Participants n=5 Participants
Sex: Female, Male Male	336 Participants n=5 Participants	343 Participants n=7 Participants	679 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	559 Participants n=5 Participants	558 Participants n=7 Participants	1117 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	79 Participants n=5 Participants	89 Participants n=7 Participants	168 Participants n=5 Participants
Race (NIH/OMB) White	463 Participants n=5 Participants	457 Participants n=7 Participants	920 Participants n=5 Participants
Race (NIH/OMB) More than one race	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	570 participants n=5 Participants	572 participants n=7 Participants	1142 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured monthly through 13 months

Population: Participants that had any follow-up data were included in analysis.

Outcome measures

Outcome measures
Measure	Azithromycin n=558 Participants Azithromycin 250 mg	Placebo n=559 Participants Inactive sugar pill
Time Until First Occurrence of Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	266 Days Interval 227.0 to 313.0	174 Days Interval 143.0 to 215.0

SECONDARY outcome

Timeframe: Measured monthly until 13 months

Population: Participants with any follow-up data were analyzed.

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 "

Outcome measures

Outcome measures
Measure	Azithromycin n=558 Participants Azithromycin 250 mg	Placebo n=559 Participants Inactive sugar pill
Exacerbations/Patient Year	1.48 exacerbations/patient year	1.83 exacerbations/patient year

SECONDARY outcome

Timeframe: Measured monthly for 12 months

Outcome measures

Outcome measures
Measure	Azithromycin n=570 Participants Azithromycin 250 mg	Placebo n=572 Participants Inactive sugar pill
Number of Emergency Department Visits as a Result of Acute Exacerbations	199 Visits	257 Visits

SECONDARY outcome

Timeframe: Measured monthly for 12 months

Outcome measures

Outcome measures
Measure	Azithromycin n=570 Participants Azithromycin 250 mg	Placebo n=572 Participants Inactive sugar pill
Number of Hospital Admissions as a Result of Acute Exacerbations	156 Hospitalizations	200 Hospitalizations

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: Participants with both baseline and one-year audiometry data available were analyzed.

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.

Outcome measures

Outcome measures
Measure	Azithromycin n=420 Participants Azithromycin 250 mg	Placebo n=426 Participants Inactive sugar pill
Change in Age-adjusted Hearing Threshold	-1.2 Decibels (db) Standard Deviation 4.2	-0.9 Decibels (db) Standard Deviation 4.1

SECONDARY outcome

Timeframe: Baseline

Population: Using cultures from participants who were not colonized with selected respiratory pathogens at the time of enrollment but who became colonized during the course of the study, samples were available from 68% of the participants in the azithromycin group and 70% in the placebo group among these cultures.

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.

Outcome measures

Outcome measures
Measure	Azithromycin n=44 Participants Azithromycin 250 mg	Placebo n=49 Participants Inactive sugar pill
Incidence of Macrolide-resistant Bacterial Colonization of the Nasopharynx or Sputum	23 Participants	28 Participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Azithromycin n=47 Participants Azithromycin 250 mg	Placebo n=108 Participants Inactive sugar pill
Incidence of Macrolide-resistant Bacterial Colonization of the Nasopharynx or Sputum	38 participants	44 participants

Adverse Events

Azithromycin

Serious events: 217 serious events

Other events: 500 other events

Deaths: 0 deaths

Placebo

Serious events: 217 serious events

Other events: 444 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Azithromycin n=570 participants at risk Azithromycin, 250 mg	Placebo n=572 participants at risk Inactive sugar pill
Respiratory, thoracic and mediastinal disorders Pneumonia	4.2% 24/570 • Number of events 26 • 13 months	6.5% 37/572 • Number of events 41 • 13 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	1.1% 6/570 • Number of events 7 • 13 months	1.4% 8/572 • Number of events 13 • 13 months
Gastrointestinal disorders Digestive	2.6% 15/570 • Number of events 15 • 13 months	3.1% 18/572 • Number of events 21 • 13 months
Cardiac disorders Circulatory	5.6% 32/570 • Number of events 32 • 13 months	5.4% 31/572 • Number of events 36 • 13 months
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	21.1% 120/570 • Number of events 145 • 13 months	19.1% 109/572 • Number of events 170 • 13 months
General disorders Other	17.5% 100/570 • Number of events 113 • 13 months	17.7% 101/572 • Number of events 114 • 13 months

Other adverse events

Other adverse events
Measure	Azithromycin n=570 participants at risk Azithromycin, 250 mg	Placebo n=572 participants at risk Inactive sugar pill
Respiratory, thoracic and mediastinal disorders Pneumonia	1.2% 7/570 • Number of events 13 • 13 months	4.2% 24/572 • Number of events 27 • 13 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	2.3% 13/570 • Number of events 13 • 13 months	2.6% 15/572 • Number of events 16 • 13 months
Gastrointestinal disorders Digestive	10.9% 62/570 • Number of events 89 • 13 months	13.6% 78/572 • Number of events 104 • 13 months
Cardiac disorders Circulatory	6.0% 34/570 • Number of events 49 • 13 months	5.1% 29/572 • Number of events 42 • 13 months
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	32.5% 185/570 • Number of events 566 • 13 months	42.7% 244/572 • Number of events 657 • 13 months
General disorders Other	56.0% 319/570 • Number of events 1132 • 13 months	57.9% 331/572 • Number of events 1176 • 13 months

Additional Information

Dr. Richard Albert

Denver Health Medical Center

Phone: 303-436-6900

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place