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The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers

Primary Purpose

Smoking

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Aclidinium bromide/formoterol fumarate dihydrate
Placebo
Sponsored by
McGill University Health Centre/Research Institute of the McGill University Health Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Smoking

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Current and former smokers with ≥20 pack-years of smoking history
  • Gas-trapping (residual volume >110% predicted)

Exclusion Criteria:

Physician-diagnosis of chronic obstructive pulmonary disease in the past 1 year and regular use of long-acting antimuscarinic (LAMA) and/or long-acting beta-agonist (LABA) (i.e., at least 30 consecutive days)

  • Physician-diagnosis of asthma in the past 5 years
  • Regular inhaled corticosteroid (ICS) use in the past 5 years (i.e., at least 30 consecutive days)
  • Physician-diagnosis of other lung diseases (sarcoidosis, tuberculosis, cystic fibrosis, pulmonary fibrosis, lung cancer), or long-term oxygen therapy
  • Respiratory tract infection within 4-weeks
  • Physician-diagnosis of arrhythmia, or significant valvular disease.
  • Physician-diagnosis of myocardial infarction, unstable angina or heart failure requiring unscheduled outpatient or emergency department visit within 6-months.
  • Arrhythmia or prolonged corrected QT (QTc) on electrocardiogram.
  • Inability to use study inhaler
  • Glaucoma
  • Benign prostatic hypertrophy
  • Pregnancy
  • Allergy to the study treatment, salbutamol, lidocaine, or severe milk protein allergy (note: lactose intolerance is not an exclusion criteria)
  • Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry
  • Inability to provide written informed consent

Sites / Locations

  • McGill University Health Centre Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active arm

Placebo arm

Arm Description

Aclidinium bromide/formoterol fumarate dihydrate 400 mcg/12 mcg Twice daily (once in the morning, once in the evening) 7-days

Placebo Twice daily (once in the morning, once in the evening) 7-days

Outcomes

Primary Outcome Measures

Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)
Mean difference in inspiratory pleural pressure measured by esophageal manometry at rest and throughout incremental exercise

Secondary Outcome Measures

Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)
Mean difference in atrial natriuretic peptide (exercise induced-changes) and n-terminal pro-B-type natriuretic peptide (resting).
Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)
Static and operating lung volumes
Effect modification by gender (self-reported).
Interaction term added to regression model for gender.
Effect modification by smoking status (self-reported).
Interaction term added to regression model for smoking status.
Effect modification by hypertension status (Joint National Committee criteria).
Interaction term added to regression model for hypertension status.
Effect modification by hyperinflation severity (Residual lung volume).
Interaction term added to regression model for hyperinflation severity.
Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7).
Interaction term added to regression model for spirometric COPD status.

Full Information

First Posted
March 29, 2017
Last Updated
April 4, 2019
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
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1. Study Identification

Unique Protocol Identification Number
NCT03104634
Brief Title
The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers
Official Title
The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers: a Randomized, Double-blind, Placebo-controlled, Cross-over Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
December 1, 2018 (Actual)
Study Completion Date
February 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This short-term study aims to prove the potential cardio-protective physiological effect of inhaled aclidinium bromide/formoterol fumarate on inspiratory pleural pressures. Smoking is associated with gas-trapping (hyperinflation), even in the absence of chronic obstructive pulmonary disease. Breathing in the presence of gas-trapping requires large negative inspiratory pleural pressures, which are transmitted to the surface of the heart and increase cardiac wall stress. Inhaled aclidinium bromide and formoterol fumarate has been shown to reduce gas-trapping, but the impact on inspiratory pleural pressures and biomarkers of cardiac stress in smokers is unknown.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoking

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Matched placebo.
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active arm
Arm Type
Experimental
Arm Description
Aclidinium bromide/formoterol fumarate dihydrate 400 mcg/12 mcg Twice daily (once in the morning, once in the evening) 7-days
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
Placebo Twice daily (once in the morning, once in the evening) 7-days
Intervention Type
Drug
Intervention Name(s)
Aclidinium bromide/formoterol fumarate dihydrate
Other Intervention Name(s)
DUAKLIR™ GENUAIR®
Intervention Description
Cross-over design with washout interval. Randomized order of active and placebo arm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo and delivery device matched to active intervention
Primary Outcome Measure Information:
Title
Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)
Description
Mean difference in inspiratory pleural pressure measured by esophageal manometry at rest and throughout incremental exercise
Time Frame
After 7-days of active or placebo drug
Secondary Outcome Measure Information:
Title
Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)
Description
Mean difference in atrial natriuretic peptide (exercise induced-changes) and n-terminal pro-B-type natriuretic peptide (resting).
Time Frame
After 7-days of active or placebo drug
Title
Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)
Description
Static and operating lung volumes
Time Frame
After 7-days of active or placebo drug
Title
Effect modification by gender (self-reported).
Description
Interaction term added to regression model for gender.
Time Frame
After 7-days of active or placebo drug
Title
Effect modification by smoking status (self-reported).
Description
Interaction term added to regression model for smoking status.
Time Frame
After 7-days of active or placebo drug
Title
Effect modification by hypertension status (Joint National Committee criteria).
Description
Interaction term added to regression model for hypertension status.
Time Frame
After 7-days of active or placebo drug
Title
Effect modification by hyperinflation severity (Residual lung volume).
Description
Interaction term added to regression model for hyperinflation severity.
Time Frame
After 7-days of active or placebo drug
Title
Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7).
Description
Interaction term added to regression model for spirometric COPD status.
Time Frame
After 7-days of active or placebo drug

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Self-reported gender
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Current and former smokers with ≥20 pack-years of smoking history Gas-trapping (residual volume >110% predicted) Exclusion Criteria: Physician-diagnosis of chronic obstructive pulmonary disease in the past 1 year and regular use of long-acting antimuscarinic (LAMA) and/or long-acting beta-agonist (LABA) (i.e., at least 30 consecutive days) Physician-diagnosis of asthma in the past 5 years Regular inhaled corticosteroid (ICS) use in the past 5 years (i.e., at least 30 consecutive days) Physician-diagnosis of other lung diseases (sarcoidosis, tuberculosis, cystic fibrosis, pulmonary fibrosis, lung cancer), or long-term oxygen therapy Respiratory tract infection within 4-weeks Physician-diagnosis of arrhythmia, or significant valvular disease. Physician-diagnosis of myocardial infarction, unstable angina or heart failure requiring unscheduled outpatient or emergency department visit within 6-months. Arrhythmia or prolonged corrected QT (QTc) on electrocardiogram. Inability to use study inhaler Glaucoma Benign prostatic hypertrophy Pregnancy Allergy to the study treatment, salbutamol, lidocaine, or severe milk protein allergy (note: lactose intolerance is not an exclusion criteria) Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry Inability to provide written informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
B M Smith, MD
Organizational Affiliation
McGill University Health Centre/Research Institute of the McGill University Health Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
McGill University Health Centre Research Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers

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