Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Assessment In a Real World Setting of the Effect of Inhaled Steroid-based Triple Therapy Versus the Combination of Tiotropium and Olodaterol on Reducing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations [AIRWISE]

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: NCT03265145
Recruitment Status : Completed
First Posted : August 29, 2017
Results First Posted : December 9, 2021
Last Update Posted : June 14, 2022
Sponsor:
Collaborator:
HealthCore-NERI
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Stiolto Respimat
Drug: ICS (Inhaled Corticosteroid) (Triple therapy)
Drug: LABA (Long-Acting Beta Agonist) (Triple therapy)
Drug: LAMA (Long-Acting Muscarinic Antagonist) (Triple therapy)
Enrollment 714
Recruitment Details This was a pragmatic randomized open label active controlled parallel group design trial conducted in a real-world, community-based practice setting. Participants were on long-acting muscarinic antagonist (LAMA), long-acting beta agonist (LABA) or Inhaled Corticosteroid (ICS)/LABA for COPD, but were determined by their physician to not be controlled on their current therapy. Subjects were randomized to either Stiolto Respimat or ICS plus LABA plus LAMA (triple therapy) for the study.
Pre-assignment Details All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Arm/Group Title Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Hide Arm/Group Description

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Period Title: Overall Study
Started 356 358
Completed [1] 285 302
Not Completed 71 56
Reason Not Completed
Protocol Violation             2             0
Adverse Event             1             0
Withdrawal by Subject             23             19
Death             12             12
Lost to Follow-up             13             9
missing end of study form, could not definitely count as completion or discontinuation             0             1
Switched back to previous medication             1             0
Did not want to take medication             1             0
Subject could not afford medication             0             1
Site closed             2             3
Incorrectly randomized             16             6
Entered into Electronic Data Capture in error             0             1
Physician Decision             0             3
Subject transferred to another facility             0             1
[1]
12 Month Study Observation Period
Arm/Group Title Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy) Total
Hide Arm/Group Description

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Total of all reporting groups
Overall Number of Baseline Participants 356 358 714
Hide Baseline Analysis Population Description
Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 356 participants 358 participants 714 participants
69.0  (9.32) 69.9  (9.81) 69.5  (9.57)
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 358 participants 714 participants
Male
181
  50.8%
174
  48.6%
355
  49.7%
Female
169
  47.5%
181
  50.6%
350
  49.0%
Missing
6
   1.7%
3
   0.8%
9
   1.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 358 participants 714 participants
Hispanic or Latino
20
   5.6%
20
   5.6%
40
   5.6%
Not Hispanic or Latino
329
  92.4%
334
  93.3%
663
  92.9%
Unknown or Not Reported
7
   2.0%
4
   1.1%
11
   1.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 358 participants 714 participants
White or Caucasian
292
  82.0%
300
  83.8%
592
  82.9%
Black or African American
42
  11.8%
38
  10.6%
80
  11.2%
Asian
6
   1.7%
7
   2.0%
13
   1.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.3%
1
   0.1%
American Indian or Alaska Native
1
   0.3%
0
   0.0%
1
   0.1%
Other
9
   2.5%
9
   2.5%
18
   2.5%
Missing
6
   1.7%
3
   0.8%
9
   1.3%
1.Primary Outcome
Title Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the 12 Month Study Period
Hide Description

Time to first moderate or severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.

Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.

Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).

Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.

Time Frame Baseline till end of study, up to 12 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.
Arm/Group Title Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Hide Arm/Group Description:

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Overall Number of Participants Analyzed 348 354
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable as the median was not reached (and neither was the Q1).
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stiolto® Respimat®, ICS Plus LABA Plus LAMA (Triple Therapy)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.87 to 1.72
Estimation Comments

Cox proportional hazards model with baseline ICS prior use as a covariate was used to estimate the hazard ratio (HR) and the two-sided 95% Wald confidence interval (CI).

Ratio: Stiolto Respimat/triple therapy.

2.Secondary Outcome
Title Annual Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
Hide Description

Annual rate of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations.

Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.

Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).

Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.

Time Frame Baseline till end of study, up to 12 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.
Arm/Group Title Stiolto® Respimat® Triple Therapy
Hide Arm/Group Description:

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients were switched to a treatment of ICS plus LABA plus LAMA (triple therapy), made up of the combination of any approved drugs that their physician chooses, for 12 months of treatment.

Overall Number of Participants Analyzed 348 354
Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per participant per year
0.36
(0.28 to 0.47)
0.26
(0.19 to 0.34)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stiolto® Respimat®, Triple Therapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted annual rate ratio
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
0.97 to 2.04
Estimation Comments Ratio: Stiolto Respimat/triple therapy
3.Secondary Outcome
Title Time to First Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over 12 Months of Treatment Pulmonary Disease
Hide Description

Time to first severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.

Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.

Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).

Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.

Time Frame Baseline till end of study, up to 12 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.
Arm/Group Title Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Hide Arm/Group Description:

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Overall Number of Participants Analyzed 348 354
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable as the median was not reached (and neither was the Q1).
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stiolto® Respimat®, ICS Plus LABA Plus LAMA (Triple Therapy)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.62 to 2.00
Estimation Comments

Cox proportional hazards model with baseline ICS prior use as a covariate was used to estimate the hazard ratio (HR) and the two-sided 95% Wald confidence interval (CI).

Ratio: Stiolto Respimat/triple therapy.

4.Secondary Outcome
Title Annual Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
Hide Description

Annual rate of severe chronic obstructive pulmonary disease (COPD) exacerbations.

Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).

Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.

Time Frame Baseline till end of study, up to 12 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.
Arm/Group Title Stiolto® Respimat® Triple Therapy
Hide Arm/Group Description:

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients were switched to a treatment of ICS plus LABA plus LAMA (triple therapy), made up of the combination of any approved drugs that their physician chooses, for 12 months of treatment.

Overall Number of Participants Analyzed 348 354
Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per participant per year
0.07
(0.04 to 0.12)
0.07
(0.04 to 0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stiolto® Respimat®, Triple Therapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted annual rate ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.58 to 2.01
Estimation Comments Ratio: Stiolto Respimat/triple therapy
5.Secondary Outcome
Title Number of Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 12 Month Observation Period
Hide Description

Number of patients with moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations over the 12 month observation period.

Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.

Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).

Time Frame 12 months after baseline.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.
Arm/Group Title Stiolto® Respimat® Triple Therapy
Hide Arm/Group Description:

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients were switched to a treatment of ICS plus LABA plus LAMA (triple therapy), made up of the combination of any approved drugs that their physician chooses, for 12 months of treatment.

Overall Number of Participants Analyzed 348 354
Measure Type: Count of Participants
Unit of Measure: Participants
73
  21.0%
62
  17.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stiolto® Respimat®, Triple Therapy
Comments A Cochran-Mantel-Haenszel (CMH) model with baseline ICS prior use as stratum was used to estimate the Risk Ratio (RR) (Stiolto Respimat versus triple therapy) of moderate or severe COPD exacerbations along with 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.89 to 1.64
Estimation Comments Ratio: Stiolto Respimat/triple therapy
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stiolto® Respimat®, Triple Therapy
Comments A Cochran-Mantel-Haenszel (CMH) model with baseline ICS prior use as stratum was used to estimate the Risk Difference (Stiolto Respimat versus triple therapy) of moderate or severe COPD exacerbations along with 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.036
Confidence Interval (2-Sided) 95%
-0.022 to 0.094
Estimation Comments Ratio: Stiolto Respimat/triple therapy
Time Frame Up to 12 months + 21 days.
Adverse Event Reporting Description

All-Cause Mortality: all randomized patients allocated to original randomized treatment group. 5 patients in each group received the wrong prescription, these were included in the actual treatment.

Adverse events (AE): all randomized patients who received a prescription of any study treatment.

Non-serious AE collection and reporting was limited to events leading to trial discontinuation, treatment discontinuation or death as this is an approved product with a known safety profile.

 
Arm/Group Title Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Hide Arm/Group Description

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.

Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.

All-Cause Mortality
Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   12/356 (3.37%)   12/358 (3.35%) 
Hide Serious Adverse Events
Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   56/325 (17.23%)   45/318 (14.15%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  0/325 (0.00%)  1/318 (0.31%) 
Leukocytosis  1  0/325 (0.00%)  1/318 (0.31%) 
Cardiac disorders     
Acute coronary syndrome  1  0/325 (0.00%)  1/318 (0.31%) 
Acute left ventricular failure  1  1/325 (0.31%)  1/318 (0.31%) 
Acute myocardial infarction  1  0/325 (0.00%)  1/318 (0.31%) 
Atrial fibrillation  1  0/325 (0.00%)  1/318 (0.31%) 
Atrioventricular block second degree  1  1/325 (0.31%)  0/318 (0.00%) 
Bradycardia  1  0/325 (0.00%)  1/318 (0.31%) 
Cardiac arrest  1  3/325 (0.92%)  1/318 (0.31%) 
Cardiac failure  1  1/325 (0.31%)  3/318 (0.94%) 
Cardiac failure acute  1  3/325 (0.92%)  0/318 (0.00%) 
Cardiac failure chronic  1  1/325 (0.31%)  0/318 (0.00%) 
Cardiac failure congestive  1  3/325 (0.92%)  1/318 (0.31%) 
Coronary artery disease  1  2/325 (0.62%)  0/318 (0.00%) 
Left ventricular failure  1  2/325 (0.62%)  0/318 (0.00%) 
Myocardial infarction  1  0/325 (0.00%)  2/318 (0.63%) 
Palpitations  1  0/325 (0.00%)  1/318 (0.31%) 
Tachycardia  1  2/325 (0.62%)  1/318 (0.31%) 
Cardio-respiratory arrest  1  1/325 (0.31%)  0/318 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  0/325 (0.00%)  1/318 (0.31%) 
Gastrointestinal disorders     
Colitis ischaemic  1  1/325 (0.31%)  0/318 (0.00%) 
Constipation  1  0/325 (0.00%)  1/318 (0.31%) 
Diarrhoea  1  0/325 (0.00%)  1/318 (0.31%) 
Gastrointestinal haemorrhage  1  0/325 (0.00%)  1/318 (0.31%) 
Melaena  1  1/325 (0.31%)  0/318 (0.00%) 
Pancreatitis  1  0/325 (0.00%)  1/318 (0.31%) 
General disorders     
Asthenia  1  0/325 (0.00%)  1/318 (0.31%) 
Chest pain  1  1/325 (0.31%)  0/318 (0.00%) 
Death  1  2/325 (0.62%)  2/318 (0.63%) 
Generalised oedema  1  1/325 (0.31%)  0/318 (0.00%) 
Malaise  1  0/325 (0.00%)  1/318 (0.31%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/325 (0.00%)  1/318 (0.31%) 
Infections and infestations     
Bacteraemia  1  1/325 (0.31%)  0/318 (0.00%) 
Bronchitis  1  1/325 (0.31%)  0/318 (0.00%) 
Bronchitis bacterial  1  0/325 (0.00%)  1/318 (0.31%) 
Cellulitis  1  2/325 (0.62%)  0/318 (0.00%) 
Escherichia sepsis  1  1/325 (0.31%)  0/318 (0.00%) 
Infective exacerbation of chronic obstructive airways disease  1  4/325 (1.23%)  1/318 (0.31%) 
Influenza  1  1/325 (0.31%)  2/318 (0.63%) 
Lower respiratory tract infection  1  1/325 (0.31%)  0/318 (0.00%) 
Parainfluenzae virus infection  1  1/325 (0.31%)  0/318 (0.00%) 
Pneumonia  1  6/325 (1.85%)  9/318 (2.83%) 
Pneumonia mycoplasmal  1  0/325 (0.00%)  1/318 (0.31%) 
Sepsis  1  4/325 (1.23%)  3/318 (0.94%) 
Septic shock  1  1/325 (0.31%)  0/318 (0.00%) 
Urinary tract infection  1  2/325 (0.62%)  0/318 (0.00%) 
Urinary tract infection viral  1  0/325 (0.00%)  1/318 (0.31%) 
COVID-19  1  1/325 (0.31%)  1/318 (0.31%) 
Injury, poisoning and procedural complications     
Fall  1  1/325 (0.31%)  0/318 (0.00%) 
Femoral neck fracture  1  0/325 (0.00%)  1/318 (0.31%) 
Femur fracture  1  0/325 (0.00%)  1/318 (0.31%) 
Head injury  1  1/325 (0.31%)  0/318 (0.00%) 
Procedural complication  1  0/325 (0.00%)  1/318 (0.31%) 
Investigations     
Blood osmolarity decreased  1  1/325 (0.31%)  0/318 (0.00%) 
Blood pressure increased  1  5/325 (1.54%)  2/318 (0.63%) 
Heart rate increased  1  2/325 (0.62%)  0/318 (0.00%) 
Troponin increased  1  1/325 (0.31%)  1/318 (0.31%) 
Metabolism and nutrition disorders     
Dehydration  1  0/325 (0.00%)  1/318 (0.31%) 
Diabetic ketoacidosis  1  1/325 (0.31%)  0/318 (0.00%) 
Hyperglycaemia  1  1/325 (0.31%)  0/318 (0.00%) 
Hyperkalaemia  1  0/325 (0.00%)  1/318 (0.31%) 
Hypoglycaemia  1  1/325 (0.31%)  0/318 (0.00%) 
Hypokalaemia  1  0/325 (0.00%)  1/318 (0.31%) 
Hyponatraemia  1  1/325 (0.31%)  2/318 (0.63%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  0/325 (0.00%)  1/318 (0.31%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer  1  0/325 (0.00%)  1/318 (0.31%) 
Chronic lymphocytic leukaemia  1  1/325 (0.31%)  0/318 (0.00%) 
Lung carcinoma cell type unspecified stage III  1  0/325 (0.00%)  1/318 (0.31%) 
Lung neoplasm malignant  1  0/325 (0.00%)  1/318 (0.31%) 
Malignant melanoma  1  1/325 (0.31%)  0/318 (0.00%) 
Plasma cell myeloma  1  0/325 (0.00%)  1/318 (0.31%) 
Small cell lung cancer  1  1/325 (0.31%)  0/318 (0.00%) 
Squamous cell carcinoma  1  0/325 (0.00%)  1/318 (0.31%) 
Squamous cell carcinoma of lung  1  1/325 (0.31%)  0/318 (0.00%) 
Nervous system disorders     
Carotid artery stenosis  1  0/325 (0.00%)  1/318 (0.31%) 
Dizziness  1  2/325 (0.62%)  1/318 (0.31%) 
Encephalopathy  1  1/325 (0.31%)  1/318 (0.31%) 
Headache  1  3/325 (0.92%)  0/318 (0.00%) 
Hemiparesis  1  0/325 (0.00%)  1/318 (0.31%) 
Ischaemic stroke  1  0/325 (0.00%)  1/318 (0.31%) 
Metabolic encephalopathy  1  1/325 (0.31%)  0/318 (0.00%) 
Polyneuropathy  1  0/325 (0.00%)  1/318 (0.31%) 
Syncope  1  3/325 (0.92%)  1/318 (0.31%) 
Toxic encephalopathy  1  0/325 (0.00%)  1/318 (0.31%) 
Transient ischaemic attack  1  0/325 (0.00%)  1/318 (0.31%) 
Psychiatric disorders     
Delirium  1  1/325 (0.31%)  0/318 (0.00%) 
Major depression  1  0/325 (0.00%)  1/318 (0.31%) 
Mental status changes  1  1/325 (0.31%)  1/318 (0.31%) 
Renal and urinary disorders     
Acute kidney injury  1  1/325 (0.31%)  0/318 (0.00%) 
End stage renal disease  1  0/325 (0.00%)  1/318 (0.31%) 
Renal disorder  1  1/325 (0.31%)  0/318 (0.00%) 
Renal failure  1  0/325 (0.00%)  1/318 (0.31%) 
Ureteric obstruction  1  1/325 (0.31%)  0/318 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  2/325 (0.62%)  7/318 (2.20%) 
Aspiration  1  0/325 (0.00%)  1/318 (0.31%) 
Chronic obstructive pulmonary disease  1  20/325 (6.15%)  19/318 (5.97%) 
Dyspnoea  1  3/325 (0.92%)  1/318 (0.31%) 
Epistaxis  1  1/325 (0.31%)  0/318 (0.00%) 
Haemoptysis  1  1/325 (0.31%)  0/318 (0.00%) 
Orthopnoea  1  1/325 (0.31%)  0/318 (0.00%) 
Pleural effusion  1  4/325 (1.23%)  2/318 (0.63%) 
Pneumonia aspiration  1  1/325 (0.31%)  0/318 (0.00%) 
Pneumothorax  1  1/325 (0.31%)  1/318 (0.31%) 
Pulmonary embolism  1  0/325 (0.00%)  1/318 (0.31%) 
Pulmonary hypertension  1  1/325 (0.31%)  0/318 (0.00%) 
Respiratory arrest  1  0/325 (0.00%)  1/318 (0.31%) 
Respiratory failure  1  3/325 (0.92%)  2/318 (0.63%) 
Surgical and medical procedures     
Transcatheter aortic valve implantation  1  0/325 (0.00%)  1/318 (0.31%) 
Vascular disorders     
Aortic stenosis  1  1/325 (0.31%)  1/318 (0.31%) 
Arteriosclerosis  1  1/325 (0.31%)  0/318 (0.00%) 
Deep vein thrombosis  1  1/325 (0.31%)  0/318 (0.00%) 
Essential hypertension  1  0/325 (0.00%)  1/318 (0.31%) 
Hypertension  1  1/325 (0.31%)  0/318 (0.00%) 
Peripheral vascular disorder  1  0/325 (0.00%)  1/318 (0.31%) 
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stiolto® Respimat® ICS Plus LABA Plus LAMA (Triple Therapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/325 (0.00%)   0/318 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03265145    
Other Study ID Numbers: 1237-0064
First Submitted: August 25, 2017
First Posted: August 29, 2017
Results First Submitted: September 29, 2021
Results First Posted: December 9, 2021
Last Update Posted: June 14, 2022