To Evaluate Effectiveness of Aclidinium Bromide/Formoterol Fumarate Dihydrate in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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ASTUTE is a pragmatic open randomised 12-week multinational trial to evaluate the effectiveness of aclidinium bromide/formoterol fumarate dihydrate fixed-dose combination compared to standard of care bronchodilators in chronic obstructive pulmonary disease.

Detailed Description
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ASTUTE is a longitudinal, randomised, multicentre, and multinational pragmatic study of patients with Chronic Obstructive Pulmonary Disease to evaluate the comparative effectiveness of Aclidinium bromide/formoterol fumarate fixed-dose combination (Duaklir™ Genuair®) and Standard of Care bronchodilators in patients treated with long acting bronchodilator monotherapies OR patients who abide to the following treatment category: patient is newly diagnosed, or naïve to maintenance therapy, or treated with short-acting bronchodilators as rescue medication, or has not been treated with long-acting bronchodilators in the last 3 months.

Official Title
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To Evaluate Effectiveness of Aclidinium Bromide/Formoterol Fumarate Dihydrate in Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Aclidinium bromide/formoterol fumarate combination
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is aged 40 years or older; Confirmed diagnosis of COPD; Spirometry performed at study entry or within the last 3 months preceding study entry with a post-bronchodilator Forced Expiratory Volume in 1 Second/Forced Vital Capacity quotient less than 0.7; Patient is a current smoker or an ex-smoker with a smoking history of ≥10 pack-years; Patient belongs to any of these treatment groups: Patient is treated by a monotherapy long-acting bronchodilator (Long-Acting Muscarinic Antagonist or Long-Acting Beta Agonist), or Naïve COPD patient, defined as: Patient is newly diagnosed, or Patient is naïve to maintenance therapy, or Patient is treated with short acting bronchodilators as rescue medication, or Patient has not been treated with long acting bronchodilators in the last 3 months. Exclusion Criteria: - Patients should not be included in the study if any of the following exclusion criteria applies: Patient changed COPD treatment regimen over the preceding 3 months; Patient treated or intended to be treated at the time of randomisation with a maintenance regimen of inhaled corticosteroids or inhaled corticosteroids-containing medications; Patient treated or intended to be treated at the time of randomisation with aclidinium bromide/formoterol fumarate dihydrate inhalation powder; Patient had a previous diagnosis of asthma or is suspected of having asthma, asthma-COPD overlap or any other chronic respiratory disease other than COPD (including severe ones, such as cystic fibrosis, pulmonary fibrosis, active neoplasm except adequately treated [no evidence of recurrence within 5 years], active tuberculosis); Patient developed a respiratory tract infection or COPD exacerbation within 6 weeks (or 3 months if an exacerbation-related hospitalisation was required) before the randomisation visit; Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, lactose monohydrate, inhaled medication, or any component thereof (including report of paradoxical bronchospasm); Patient has been previously enrolled in the current study. Any condition that in the Investigator's opinion, would limit a patient's ability to participate in the study.

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 |
| --- | --- |
| Active Comparator: Aclidinium/formoterol<br>Patients will be randomized to receive either Aclidinium bromide/formoterol fumarate fixed-dose combination | Drug: Aclidinium bromide/formoterol fumarate combination<br>* Patients will be randomized to receive either Aclidinium bromide/formoterol fumarate fixed-dose combination (Duaklir™ Genuair®), or Standard Of Care (SOC) Bronchodilators. The product in study is Aclidinium bromide/formoterol fumarate fixed-dose combination (Duaklir™ Genuair®). Each inhaler will contain at least 60 doses (and a maximum of 68 doses) of aclidinium bromide/formoterol fixed-dose combination 400μg /12μg. Patients will be instructed to take 1 puff in the morning (09:00 ± 1 h) and 1 puff in the evening (21:00 ± 1 h) during the 12 weeks of treatment.<br>* Other names: Duaklir™ Genuair®;|
| Active Comparator: Bronchodilators<br>The comparator arm consists of SOC. | Drug: Standard of Care<br>* Brochodilators<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in overall early morning COPD symptom severity score of aclidinium bromide/formoterol fumarate dihydrate inhalation powder vs. Standard of Care bronchodilators as measured by the Early Morning Symptoms of COPD Instrument over 12 wks. | Changes from baseline compared between aclidinium bromide/formoterol fumarate dihydrate inhalation powder and Standard of Care bronchodilators. Baseline values for EMSCI will be averaged over the study entry and previous day. For longitudinal analyses, each daily measure will be aggregated on a weekly (7 days) basis during the weeks of measurement (weeks 4, 8, and/or 12) by taking the mean value of all available measurements during the week. | study entry and previous day (retrospectively), days 22-28, days 50-56, days 78-84 | 
| Change from baseline in overall night time COPD symptom severity score of aclidinium bromide/formoterol fumarate dihydrate inhalation powder vs. Standard of Care bronchodilators as measured by the Nighttime Symptoms of COPD Instrument over 12 weeks. | Changes from baseline compared between aclidinium bromide/formoterol fumarate dihydrate inhalation powder and Standard of Care bronchodilators. Baseline values for NiSCI will be averaged over the study entry and previous day. For longitudinal analyses, each daily measure will be aggregated on a weekly (7 days) basis during the weeks of measurement (weeks 4, 8, and/or 12) by taking the mean value of all available measurements during the week. | study entry and previous day (retrospectively), days 22-28, days 50-56, days 78-84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in daily RS total Score of aclidinium bromide/formoterol fumarate dihydrate inhalation powder versus Standard of Care bronchodilators measured by the E-RS™COPD scale over 12 weeks. | Baseline values of the RS-Total Score will be collected and averaged at the study entry visit and previous day. The secondary effectiveness variable will be estimated by the change from baseline in daily RS-Total Score over 12 weeks of treatment. | study entry and previous day (retrospectively), days 22-28, days 50-56, days 78-84 | 
| Change from baseline in health status of aclidinium bromide/formoterol fumarate dihydrate inhalation powder versus Standard of Care bronchodilatorsmeasured by the COPD assessment Test (CAT) over 12 weeks. | The CAT measures the health status of patients with COPD. If the response to 1 of the 8 items is missing, the score will be considered missing. Change from baseline in health status over 12 weeks of follow-up (on the last day of weeks 4, 8, and 12) will be calculated. These change scores will be the CAT endpoint. | study entry, days 28, 56 and 84 | 
| Change from baseline in total time index of aclidinium bromide/formoterol fumarate dihydrate inhalation powder versus Standard of Care bronchodilators measured by the Yale Physical Activity Survey (YPAS) over 12 weeks. | The Total Time Index will be calculated at baseline and over 12 weeks of follow-up (on the last day of weeks 4, 8, and 12). Change from baseline will be calculated. These change scores will be the Total Time Index analysed. | study entry, days 28, 56 and 84 | 
| Change from baseline in Energy Expenditure Index of aclidinium bromide/formoterol fumarate dihydrate inhalation powder versus Standard of Care bronchodilators measured by the Yale Physical Activity Survey (YPAS) over 12 weeks. | The Energy Expenditure Index will be calculated at baseline and over 12 weeks of follow-up (on the last day of weeks 4, 8, and 12). Change from baseline will be calculated. These change scores will be the Energy Expenditure Index analysed. | study entry, days 28, 56 and 84 | 
| Change from baseline in Activity Dimensions Summary Index of aclidinium bromide/formoterol fumarate dihydrate inhalation powder versus Standard of Care bronchodilators measured by the Yale Physical Activity Survey (YPAS) over 12 weeks. | The Activity Dimensions Summary Index will be calculated at baseline and over 12 weeks of follow-up (on the last day of weeks 4, 8, and 12). Change from baseline will be calculated. These change scores will be the Activity Dimensions Summary Index analysed. | study entry, days 28, 56 and 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomised, Pragmatic, Standard of Care, Aclidinium bromide/formoterol fumarate fixed-dose combination, Duaklir, Genuair, ASTUTE, Chronic Obstructive Pulmonary Disease