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]

Study Overview
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Brief Summary
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The primary objective of this pragmatic study is to compare the time to first moderate or severe COPD exacerbation in patients, not controlled on their current therapy, randomized to Stiolto Respimat versus triple therapy over 12 months of treatment The secondary objectives of this study include: To compare the annual rate of moderate or severe COPD exacerbations for patients on Stiolto Respimat with patients on triple therapy. To compare the time to first severe COPD exacerbation in both treatment arms. To compare the annual rate of severe COPD exacerbations in both treatment arms. To compare the proportion of patients with moderate or severe COPD exacerbations in both treatment arms.

Official Title
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Randomized Pragmatic Clinical Trial in a Community-Based Setting Comparing STIOLTO® RESPIMAT® vs. ICS-LABA Plus LAMA in Patients With COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD diagnosis as defined by the study physician Currently on one of the following maintenance therapies: LAMA monotherapy LABA monotherapy ICS/LABA (FDC) Physician determination that patient is not controlled on current pharmacotherapy Adult patient 40 years of age or older at time of study enrollment Willingness and ability to understand and provide documented Informed Consent Form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) Authorization Form prior to commencement of any study required assessments, either directly or through Legally Authorized Representative. Exclusion Criteria: Currently on LAMA/LABA (free or FDC) or triple therapy (ICS plus LABA plus LAMA) Contraindication to any study medications (LAMA, LABA or ICS) Documented diagnosis of current asthma Pregnant or nursing women Women of childbearing potential are not restricted in this trial, however it is expected that the investigator will assess the risks and benefits of the assigned treatment as per the product label(s) and discuss this with any women of childbearing potential prior to providing the patient with the prescription for the assigned treatment.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stiolto Respimat<br> | Drug: Stiolto Respimat<br>* Duration - 12 months<br>* Other names: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO;|
| Active Comparator: ICS plus LABA plus LAMA (triple therapy)<br>ICS (Inhaled Corticosteroid) plus LABA (Long-Acting Beta Agonist) plus (Long-Acting Muscarinic Antagonist) | Drug: ICS (Inhaled Corticosteroid) (Triple therapy)<br>* Duration - 12 months<br>Drug: LABA (Long-Acting Beta Agonist) (Triple therapy)<br>* Duration - 12 months<br>Drug: LAMA (Long-Acting Muscarinic Antagonist) (Triple therapy)<br>* Duration - 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the 12 Month Study Period | 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. | Baseline till end of study, up to 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | 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. | Baseline till end of study, up to 12 months. | 
| Time to First Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over 12 Months of Treatment Pulmonary Disease | 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. | Baseline till end of study, up to 12 months. | 
| Annual Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | 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. | Baseline till end of study, up to 12 months. | 
| Number of Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 12 Month Observation Period | 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). | 12 months after baseline. |