Trial Outcomes & Findings for Comparative Effectiveness and Safety of Inhaled Corticosteroids and Antimicrobial Compounds for Non-CF Bronchiectasis (NCT NCT02714283)
NCT ID: NCT02714283
Last Updated: 2019-09-18
Results Overview
Incidence of treated pulmonary nontuberculous mycobacterium (NTM) disease
Recruitment status
COMPLETED
Target enrollment
90089 participants
Primary outcome timeframe
up to 8 years
Results posted on
2019-09-18
Participant Flow
Complete national 2006-2014 Medicare data from Part A, B and D (but not C) were obtained from Center for Medicare and Medicaid Services for patients with ICD-9-CM code 494.0 or 494.1 (bronchiectasis without or with acute exacerbation).
From the identified bronchiectasis cohort, we excluded patients with cystic fibrosis, HIV infection, or a history of organ transplant. Such patients are fundamentally different than non-CF bronchiectasis patients who lack these factors with regard to their risk for infection, hospitalization, and many of the outcomes under study in this proposal.
Participant milestones
| Measure |
Inhaled Corticosteroids (ICS)
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Overall Study
STARTED
|
83589
|
6500
|
|
Overall Study
COMPLETED
|
83589
|
6500
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparative Effectiveness and Safety of Inhaled Corticosteroids and Antimicrobial Compounds for Non-CF Bronchiectasis
Baseline characteristics by cohort
| Measure |
Inhaled Corticosteroids (ICS)
n=83589 Participants
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=6500 Participants
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
Total
n=90089 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
83589 Participants
n=5 Participants
|
6500 Participants
n=7 Participants
|
90089 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
56583 Participants
n=5 Participants
|
4750 Participants
n=7 Participants
|
61333 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27006 Participants
n=5 Participants
|
1750 Participants
n=7 Participants
|
28756 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska native
|
362 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
379 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian/Pacific Islander
|
3353 Participants
n=5 Participants
|
160 Participants
n=7 Participants
|
3513 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African-American
|
5338 Participants
n=5 Participants
|
236 Participants
n=7 Participants
|
5574 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
5188 Participants
n=5 Participants
|
203 Participants
n=7 Participants
|
5391 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White (non-Hispanic)
|
68508 Participants
n=5 Participants
|
5820 Participants
n=7 Participants
|
74328 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other/Unknown
|
840 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
904 Participants
n=5 Participants
|
|
Region of Enrollment
United States · Midwest
|
17129 Participants
n=5 Participants
|
1612 Participants
n=7 Participants
|
18741 Participants
n=5 Participants
|
|
Region of Enrollment
United States · Northeast
|
18629 Participants
n=5 Participants
|
992 Participants
n=7 Participants
|
19621 Participants
n=5 Participants
|
|
Region of Enrollment
United States · South
|
33289 Participants
n=5 Participants
|
2897 Participants
n=7 Participants
|
36186 Participants
n=5 Participants
|
|
Region of Enrollment
United States · West
|
14542 Participants
n=5 Participants
|
999 Participants
n=7 Participants
|
15541 Participants
n=5 Participants
|
|
Residential category
Rural
|
65261 Participants
n=5 Participants
|
4798 Participants
n=7 Participants
|
70059 Participants
n=5 Participants
|
|
Residential category
Metropolitan
|
18328 Participants
n=5 Participants
|
1702 Participants
n=7 Participants
|
20030 Participants
n=5 Participants
|
|
Physician encounters in the 12 month prior to Baseline
0-7
|
24345 Participants
n=5 Participants
|
1482 Participants
n=7 Participants
|
25827 Participants
n=5 Participants
|
|
Physician encounters in the 12 month prior to Baseline
8-12
|
20027 Participants
n=5 Participants
|
1526 Participants
n=7 Participants
|
21553 Participants
n=5 Participants
|
|
Physician encounters in the 12 month prior to Baseline
13-19
|
20549 Participants
n=5 Participants
|
1771 Participants
n=7 Participants
|
22320 Participants
n=5 Participants
|
|
Physician encounters in the 12 month prior to Baseline
20+
|
18668 Participants
n=5 Participants
|
1721 Participants
n=7 Participants
|
20389 Participants
n=5 Participants
|
|
Pulmonologist encounters in the prior 12 months before baseline
0
|
19013 Participants
n=5 Participants
|
692 Participants
n=7 Participants
|
19705 Participants
n=5 Participants
|
|
Pulmonologist encounters in the prior 12 months before baseline
1
|
15157 Participants
n=5 Participants
|
941 Participants
n=7 Participants
|
16098 Participants
n=5 Participants
|
|
Pulmonologist encounters in the prior 12 months before baseline
2
|
15437 Participants
n=5 Participants
|
1032 Participants
n=7 Participants
|
16469 Participants
n=5 Participants
|
|
Pulmonologist encounters in the prior 12 months before baseline
3
|
11025 Participants
n=5 Participants
|
1005 Participants
n=7 Participants
|
12030 Participants
n=5 Participants
|
|
Pulmonologist encounters in the prior 12 months before baseline
4
|
7232 Participants
n=5 Participants
|
724 Participants
n=7 Participants
|
7956 Participants
n=5 Participants
|
|
Pulmonologist encounters in the prior 12 months before baseline
5+
|
15725 Participants
n=5 Participants
|
2106 Participants
n=7 Participants
|
17831 Participants
n=5 Participants
|
|
Inpatient admissions in the 12 months prior to baseline
0
|
49795 Participants
n=5 Participants
|
4108 Participants
n=7 Participants
|
53903 Participants
n=5 Participants
|
|
Inpatient admissions in the 12 months prior to baseline
1
|
17943 Participants
n=5 Participants
|
1299 Participants
n=7 Participants
|
19242 Participants
n=5 Participants
|
|
Inpatient admissions in the 12 months prior to baseline
2+
|
15851 Participants
n=5 Participants
|
1093 Participants
n=7 Participants
|
16944 Participants
n=5 Participants
|
|
Hospitalized respiratory infections in the 12 months prior to baseline
|
9583 Participants
n=5 Participants
|
885 Participants
n=7 Participants
|
10468 Participants
n=5 Participants
|
|
Number of acute respiratory infections in the 12 months prior to baseline
0
|
40746 Participants
n=5 Participants
|
2478 Participants
n=7 Participants
|
43224 Participants
n=5 Participants
|
|
Number of acute respiratory infections in the 12 months prior to baseline
1
|
20193 Participants
n=5 Participants
|
1384 Participants
n=7 Participants
|
21577 Participants
n=5 Participants
|
|
Number of acute respiratory infections in the 12 months prior to baseline
2-3
|
15993 Participants
n=5 Participants
|
1499 Participants
n=7 Participants
|
17492 Participants
n=5 Participants
|
|
Number of acute respiratory infections in the 12 months prior to baseline
4+
|
6657 Participants
n=5 Participants
|
1139 Participants
n=7 Participants
|
7796 Participants
n=5 Participants
|
|
Comorbidities (any history)
Allergic bronchopulmonary aspergillosis
|
854 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
918 Participants
n=5 Participants
|
|
Comorbidities (any history)
Alpha-1 antitrypsin deficiency
|
292 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
335 Participants
n=5 Participants
|
|
Comorbidities (any history)
Asthma
|
33480 Participants
n=5 Participants
|
1795 Participants
n=7 Participants
|
35275 Participants
n=5 Participants
|
|
Comorbidities (any history)
COPD/emphysema
|
70548 Participants
n=5 Participants
|
5050 Participants
n=7 Participants
|
75598 Participants
n=5 Participants
|
|
Comorbidities (any history)
Interstitial lung disease
|
5526 Participants
n=5 Participants
|
507 Participants
n=7 Participants
|
6033 Participants
n=5 Participants
|
|
Comorbidities (any history)
Lung cancer
|
3497 Participants
n=5 Participants
|
196 Participants
n=7 Participants
|
3693 Participants
n=5 Participants
|
|
Comorbidities (any history)
NTM History
|
3164 Participants
n=5 Participants
|
1307 Participants
n=7 Participants
|
4471 Participants
n=5 Participants
|
|
Comorbidities (any history)
Primary ciliary dyskinesia
|
141 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
164 Participants
n=5 Participants
|
|
Comorbidities (any history)
Primary immune deficiency
|
3857 Participants
n=5 Participants
|
466 Participants
n=7 Participants
|
4323 Participants
n=5 Participants
|
|
Comorbidities (any history)
Pseudomonas infection
|
5123 Participants
n=5 Participants
|
810 Participants
n=7 Participants
|
5933 Participants
n=5 Participants
|
|
Comorbidities (any history)
Silicosis
|
103 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Adapted Charlson comorbidity index (prior 12 months)
0
|
20514 Participants
n=5 Participants
|
1534 Participants
n=7 Participants
|
22048 Participants
n=5 Participants
|
|
Adapted Charlson comorbidity index (prior 12 months)
1
|
33959 Participants
n=5 Participants
|
3119 Participants
n=7 Participants
|
37078 Participants
n=5 Participants
|
|
Adapted Charlson comorbidity index (prior 12 months)
2+
|
29116 Participants
n=5 Participants
|
1847 Participants
n=7 Participants
|
30963 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 8 yearsPopulation: Analysis population excluded all patients with a history of NTM treatment or diagnosis prior to exposure start.
Incidence of treated pulmonary nontuberculous mycobacterium (NTM) disease
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=19460 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=1736 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Nontuberculous Mycobacterial (NTM) Disease
|
188 Events
|
32 Events
|
PRIMARY outcome
Timeframe: up to 8 yearsAmong a national cohort of non-CF bronchiectasis patients, we will compare the effectiveness of corticosteroid and macrolide therapy with regards to prevention of hospitalized respiratory infection.
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=33328 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=3068 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Hospitalized Respiratory Infection
|
4213 Events
|
317 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsMyocardial infarction event
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=34688 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=3171 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Sudden Cardiac Arrest
|
892 Events
|
81 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsSensorineural hearing loss.
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=33491 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=2993 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Sensorineural Hearing Loss
|
2574 Events
|
347 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsHip fracture.
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=34661 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=3173 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Hip Fracture
|
919 Events
|
77 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsOpportunistic infections.
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=34200 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=3113 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Opportunistic Infections
|
1585 Events
|
180 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsAll-cause mortality.
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=34912 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=3193 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
All-cause Mortality
|
3362 Events
|
270 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsAll-cause hospitalization.
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=28882 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=2729 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
All-cause Hospitalization
|
17939 Events
|
1352 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsHemoptysis event
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=34835 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=3185 Patient-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Hemoptysis
|
253 Events
|
31 Events
|
SECONDARY outcome
Timeframe: up to 8 yearsArrhythmia (principal diagnosis)
Outcome measures
| Measure |
Inhaled Corticosteroids (ICS)
n=31395 person-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists.
|
Macrolide Monotherapy
n=2855 person-years
New use was defined as the first prescription for a minimum 28 day ("chronic") supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded.
|
|---|---|---|
|
Arrhythmia
|
9508 events
|
728 events
|
Adverse Events
Non-CF Bronchiectasis Patients on ICS Monotherapy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Emily Henkle, PhD, MPH
Oregon Health & Science University
Phone: 503-494-6226
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place