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Comparative Effectiveness and Safety of Inhaled Corticosteroids and Antimicrobial Compounds for Non-CF Bronchiectasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02714283
Recruitment Status : Completed
First Posted : March 21, 2016
Results First Posted : July 12, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
University of Alabama at Birmingham
National Jewish Health
COPD Foundation
Information provided by (Responsible Party):
Kevin Winthrop, Oregon Health and Science University

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Retrospective
Condition Bronchiectasis
Interventions Drug: inhaled corticosteroid therapy
Drug: macrolide therapy
Enrollment 90089
Recruitment Details 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).
Pre-assignment Details 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.
Arm/Group Title Inhaled Corticosteroids (ICS) Macrolide Monotherapy
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started [1] 83589 6500
Completed [2] 83589 6500
Not Completed 0 0
[1]
Treatment episode start
[2]
Earliest date: death, 1st outcome occurrence, study end, lost coverage, treatment stop or switch
Arm/Group Title Inhaled Corticosteroids (ICS) Macrolide Monotherapy Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 83589 6500 90089
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
83589
 100.0%
6500
 100.0%
90089
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
Female
56583
  67.7%
4750
  73.1%
61333
  68.1%
Male
27006
  32.3%
1750
  26.9%
28756
  31.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
American Indian or Alaska native
362
   0.4%
17
   0.3%
379
   0.4%
Asian/Pacific Islander
3353
   4.0%
160
   2.5%
3513
   3.9%
Black or African-American
5338
   6.4%
236
   3.6%
5574
   6.2%
Hispanic
5188
   6.2%
203
   3.1%
5391
   6.0%
White (non-Hispanic)
68508
  82.0%
5820
  89.5%
74328
  82.5%
Other/Unknown
840
   1.0%
64
   1.0%
904
   1.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 83589 participants 6500 participants 90089 participants
Midwest
17129
  20.5%
1612
  24.8%
18741
  20.8%
Northeast
18629
  22.3%
992
  15.3%
19621
  21.8%
South
33289
  39.8%
2897
  44.6%
36186
  40.2%
West
14542
  17.4%
999
  15.4%
15541
  17.3%
Residential category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
Rural
65261
  78.1%
4798
  73.8%
70059
  77.8%
Metropolitan
18328
  21.9%
1702
  26.2%
20030
  22.2%
Physician encounters in the 12 month prior to Baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
0-7
24345
  29.1%
1482
  22.8%
25827
  28.7%
8-12
20027
  24.0%
1526
  23.5%
21553
  23.9%
13-19
20549
  24.6%
1771
  27.2%
22320
  24.8%
20+
18668
  22.3%
1721
  26.5%
20389
  22.6%
Pulmonologist encounters in the prior 12 months before baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
0
19013
  22.7%
692
  10.6%
19705
  21.9%
1
15157
  18.1%
941
  14.5%
16098
  17.9%
2
15437
  18.5%
1032
  15.9%
16469
  18.3%
3
11025
  13.2%
1005
  15.5%
12030
  13.4%
4
7232
   8.7%
724
  11.1%
7956
   8.8%
5+
15725
  18.8%
2106
  32.4%
17831
  19.8%
Inpatient admissions in the 12 months prior to baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
0
49795
  59.6%
4108
  63.2%
53903
  59.8%
1
17943
  21.5%
1299
  20.0%
19242
  21.4%
2+
15851
  19.0%
1093
  16.8%
16944
  18.8%
Hospitalized respiratory infections in the 12 months prior to baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
9583
  11.5%
885
  13.6%
10468
  11.6%
Number of acute respiratory infections in the 12 months prior to baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
0
40746
  48.7%
2478
  38.1%
43224
  48.0%
1
20193
  24.2%
1384
  21.3%
21577
  24.0%
2-3
15993
  19.1%
1499
  23.1%
17492
  19.4%
4+
6657
   8.0%
1139
  17.5%
7796
   8.7%
Comorbidities (any history)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
Allergic bronchopulmonary aspergillosis
854
   1.0%
64
   1.0%
918
   1.0%
Alpha-1 antitrypsin deficiency
292
   0.3%
43
   0.7%
335
   0.4%
Asthma
33480
  40.1%
1795
  27.6%
35275
  39.2%
COPD/emphysema
70548
  84.4%
5050
  77.7%
75598
  83.9%
Interstitial lung disease
5526
   6.6%
507
   7.8%
6033
   6.7%
Lung cancer
3497
   4.2%
196
   3.0%
3693
   4.1%
NTM History
3164
   3.8%
1307
  20.1%
4471
   5.0%
Primary ciliary dyskinesia
141
   0.2%
23
   0.4%
164
   0.2%
Primary immune deficiency
3857
   4.6%
466
   7.2%
4323
   4.8%
Pseudomonas infection
5123
   6.1%
810
  12.5%
5933
   6.6%
Silicosis
103
   0.1%
6
   0.1%
109
   0.1%
Adapted Charlson comorbidity index (prior 12 months)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83589 participants 6500 participants 90089 participants
0
20514
  24.5%
1534
  23.6%
22048
  24.5%
1
33959
  40.6%
3119
  48.0%
37078
  41.2%
2+
29116
  34.8%
1847
  28.4%
30963
  34.4%
[1]
Measure Description:

Charlson comorbidity index, higher score is worse. References for the Deyo adapted Charlson comorbidity index. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. Journal of clinical epidemiology. 1992;45(6):613-9. PubMed PMID: 1607900.

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of chronic diseases. 1987;40(5):373-83. PubMed PMID: 3558716.

1.Primary Outcome
Title Nontuberculous Mycobacterial (NTM) Disease
Hide Description Incidence of treated pulmonary nontuberculous mycobacterium (NTM) disease
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population excluded all patients with a history of NTM treatment or diagnosis prior to exposure start.
Arm/Group Title Inhaled Corticosteroids (ICS) Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 16136 1496
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
19460 1736
Measure Type: Number
Unit of Measure: Events
188 32
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inhaled Corticosteroids (ICS), Macrolide Monotherapy
Comments Due to the small sample size in the macrolide monotherapy group, for this outcome, the results are considered exploratory/descriptive only.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.51 to 1.14
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
2.Primary Outcome
Title Hospitalized Respiratory Infection
Hide Description Among 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.
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
33328 3068
Measure Type: Number
Unit of Measure: Events
4213 317
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
1.23 to 1.57
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
3.Secondary Outcome
Title Sudden Cardiac Arrest
Hide Description Myocardial infarction event
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
34688 3171
Measure Type: Number
Unit of Measure: Events
892 81
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.67 to 1.09
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
4.Secondary Outcome
Title Sensorineural Hearing Loss
Hide Description Sensorineural hearing loss.
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
Patients prescribed a 28 day or more supply of ICS, with an absence of ICS prescriptions for at least the 12 months prior to identified prescription. ICS include beclomethasone, budesonide, flunisolide, fluticasone, mometasone, triamcinolone, ipratropium/albuterol, budesonide/formoterol, or fluticasone/salmeterol. Exclude baseline 28+ day macrolide, missing geographic or socioeconomic data.
Patients prescribed a 28 day or more supply of a macrolide, with an absence of macrolide prescriptions for at least the 12 months prior to identified prescription. Macrolides include oral azithromycin, clarithromycin, and erythromycin. Exclude baseline 28+ day ICS, missing geographic or socioeconomic data
Overall Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
33491 2993
Measure Type: Number
Unit of Measure: Events
2574 347
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.64 to 0.82
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
5.Secondary Outcome
Title Hip Fracture
Hide Description Hip fracture.
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
34661 3173
Measure Type: Number
Unit of Measure: Events
919 77
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.80 to 1.32
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
6.Secondary Outcome
Title Opportunistic Infections
Hide Description Opportunistic infections.
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
34200 3113
Measure Type: Number
Unit of Measure: Events
1585 180
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.76 to 1.07
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
7.Secondary Outcome
Title All-cause Mortality
Hide Description All-cause mortality.
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
34912 3193
Measure Type: Number
Unit of Measure: Events
3362 270
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.96 to 1.25
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
8.Secondary Outcome
Title All-cause Hospitalization
Hide Description All-cause hospitalization.
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
28882 2729
Measure Type: Number
Unit of Measure: Events
17939 1352
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
1.08 to 1.21
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
9.Secondary Outcome
Title Hemoptysis
Hide Description Hemoptysis event
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-years
34835 3185
Measure Type: Number
Unit of Measure: Events
253 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.66 to 1.51
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
10.Secondary Outcome
Title Arrhythmia
Hide Description Arrhythmia (principal diagnosis)
Time Frame up to 8 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 83495 6498
Overall Number of Units Analyzed
Type of Units Analyzed: Person-years
31395 2855
Measure Type: Number
Unit of Measure: events
9508 728
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-CF Bronchiectasis Patients on ICS Monotherapy, Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for propensity score decile, oral corticosteroid use, and NTM history
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
1.07 to 1.25
Estimation Comments ICS (numerator) compared to macrolide monotherapy (denominator)
Time Frame This is a retrospective observational study. Only medical history data was collected.
Adverse Event Reporting Description All-Cause Mortality, Serious, and Other Adverse Events were not monitored. We report Safety Outcomes in the Outcomes section.
 
Arm/Group Title Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Hide Arm/Group Description Patients prescribed a 28 day or more supply of ICS, with an absence of ICS prescriptions for at least the 12 months prior to identified prescription. ICS include beclomethasone, budesonide, flunisolide, fluticasone, mometasone, triamcinolone, ipratropium/albuterol, budesonide/formoterol, or fluticasone/salmeterol. Exclude baseline 28+ day macrolide, missing geographic or socioeconomic data. Patients prescribed a 28 day or more supply of a macrolide, with an absence of macrolide prescriptions for at least the 12 months prior to identified prescription. Macrolides include oral azithromycin, clarithromycin, and erythromycin. Exclude baseline 28+ day ICS, missing geographic or socioeconomic data
All-Cause Mortality
Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
Show Serious Adverse Events Hide Serious Adverse Events
Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Non-CF Bronchiectasis Patients on ICS Monotherapy Non-CF Bronchiectasis Patients on Macrolide Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
Claims-based data limits our ability to confirm bronchiectasis diagnoses and include disease symptoms/severity in our models. Results may not be applicable to <65 year old bronchiectasis patients who have a lower underlying risk of pneumonia.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Emily Henkle, PhD, MPH
Organization: Oregon Health & Science University
Phone: 503-494-6226
Responsible Party: Kevin Winthrop, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT02714283     History of Changes
Other Study ID Numbers: CER-1503-29191
First Submitted: March 15, 2016
First Posted: March 21, 2016
Results First Submitted: October 1, 2018
Results First Posted: July 12, 2019
Last Update Posted: July 12, 2019