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

NCT03104634 | Completed Phase 3

• 1 other identifier: 2017-2748
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Smoking

Outcome Measures

Primary Outcomes (1)

• 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

  After 7-days of active or placebo drug

Secondary Outcomes (7)

• Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)

  After 7-days of active or placebo drug

• Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)

  After 7-days of active or placebo drug

• Effect modification by gender (self-reported).

  After 7-days of active or placebo drug

• Effect modification by smoking status (self-reported).

  After 7-days of active or placebo drug

• Effect modification by hypertension status (Joint National Committee criteria).

  After 7-days of active or placebo drug

Study Arms (2)

Active arm

EXPERIMENTAL

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

Drug: Aclidinium bromide/formoterol fumarate dihydrate

Placebo arm

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Aclidinium bromide/formoterol fumarate dihydrate DRUG

Cross-over design with washout interval. Randomized order of active and placebo arm

Also known as: DUAKLIR™ GENUAIR®

Active arm

Placebo DRUG

Placebo and delivery device matched to active intervention

Placebo arm

Eligibility Criteria

• Age: 45 Years - 75 Years
• Gender Eligibility Details: Self-reported gender
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry
• Inability to provide written informed consent

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Centre Research Institute

Montreal, Quebec, H4A 3J1, Canada

Location

MeSH Terms

Conditions

Smoking

Interventions

aclidinium bromide

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• B M Smith, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matched placebo.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 7, 2017
• Study Start: May 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: February 1, 2019
• Last Updated: April 8, 2019

Record last verified: 2019-04

Locations

CA (1)