COPDPhase 3NCT01491802
Effect of a New Combination Bronchodilator on Exercise in GOLD Stage II Moderate COPD
A Phase 3 study testing LAMA/LABA and LAMA in people with COPD, run by Queen's University at 1 site in Canada.
Trial summary
Preliminary information from our laboratory indicated that even patients with milder chronic obstructive pulmonary disease (COPD) can have significant physiological derangements which become more pronounced during exercise, leading to intolerable dyspnea at lower levels of ventilation than in health. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD
- What is being tested?
- LAMA/LABA and LAMA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2012to Sep 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stable moderate COPD
- Post-bronchodilator FEV1/FVC<0.7 and 50%≤FEV1<80% predicted
- Baseline Dyspnea Index ≤ 9 and MRC dyspnea scale >2
- Cigarette smoking history at least 20 pack-years
Who cannot join
- Presence of a significant disease other than COPD that could contribute to dyspnea and exercise limitation
- Important contraindications to clinical exercise testing
- Use of daytime oxygen
- History of asthma
Trial locations and contacts
1 site in 1 country.
Canada1 site
Respiratory Investigation Unit at Kingston General Hospital
Kingston, Ontario, K7L 2V7
About this study
Official title: A 4-week Randomized, Double-blind, Crossover Study to Assess the Effect of a New LABA/LAMA Combination Versus LAMA Alone on Exertional Dyspnea, Exercise Endurance and Neuromechanical Coupling in Patients With GOLD Stage II COPD
Preliminary information from our laboratory indicated that even patients with milder chronic obstructive pulmonary disease (COPD) can have significant physiological derangements which become more pronounced during exercise, leading to intolerable dyspnea at lower levels of ventilation than in health. This study will explore pathophysiological mechanisms of dyspnea and activity limitation in GOLD stage II COPD and will determine if there is a sound physiological rationale for the use of dual long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) therapy (GSK573719/ GW642444 Inhalation Powder) versus LAMA alone (GSK573719) as treatment for dyspnea and exercise intolerance in this subpopulation. Objectives of this study are to determine if: 1) neuromechanical uncoupling of the respiratory system contributes to exertional dyspnea in milder COPD, and 2) treatment with LABA/LAMA improves dyspnea and exercise endurance compared with LAMA by improving neuromechanical coupling. The investigators hypothesize that: 1) dyspnea is related to excessive dynamic lung hyperinflation, tidal volume restriction and increased ratio of central respiratory neural drive to tidal volume displacement, a measure of neuromechanical uncoupling of the respiratory system, and 2) LABA/LAMA will improve dyspnea and exercise endurance, which will be explained by partial reversal of the above mechanical abnormalities. The investigators will conduct a randomized, double-blind crossover study and compare the effects of once-daily LABA/LAMA over 4-weeks with LAMA on dyspnea, exercise endurance and ventilatory mechanics in GOLD stage II COPD.
- Conditions
- COPD
- Being tested
- LAMA/LABA, LAMA
- Keywords
- COPD, Combination therapy, Anticholinergic, Beta2-agonist, Exercise, Dyspnea, Respiratory mechanics
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Motor Activity, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAMA/LABADrug
Also called GSK573719+GW642444, umeclidinium (GSK573719) / vilanterol (GW642444), Anoro ELLIPTA
GSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy will be taken once daily for 4 weeks.
LAMADrug
Also called umeclidinium
GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| LAMA alone, then LAMA/LABA combination | Experimental | Participants will first receive an inhaled long-acting muscarinic antagonist (LAMA) once daily for 4 weeks. After a 2 week washout period, they will then receive the fixed-dose combination product [LAMA plus long-acting beta2-agonist (LABA)] once daily for 4 weeks. Receives: Drug: LAMA/LABA; Drug: LAMA |
| LABA/LAMA combination, then LAMA alone | Experimental | Participants will first receive a long-acting muscarinic antagonist (LAMA) plus long-acting beta2-agonist (LABA) combination product once daily for 4 weeks. After a 2 week washout period, they will then receive the LAMA single product once daily for 4 weeks. Receives: Drug: LAMA/LABA; Drug: LAMA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exertional Dyspnea Intensity at Isotime Exercise.
Intensity of dyspnea (defined as breathing discomfort) at a standardized time (isotime) during constant work rate exercise tests as measured by the modified 10-point Borg scale. A rating of 0 represents no dyspnea up to a maximum of 10: a smaller rating is therefore an improvement. Isotime was defined as the highest exercise time in minutes completed in both post-treatment tests.
Measured: 4 weeks
Secondary outcomes (9)
Exercise Endurance Time
Duration of constant work rate cycle exercise at 75% of maximum
Measured: 4 weeks
Inspiratory Capacity at Rest
Measurements of pulmonary function included spirometry and body plethysmography. The resting inspiratory capacity (IC) values reported here are 90 minutes post-dose after 4 weeks of treatment.
Measured: 4 weeks
Ventilation at Isotime Exercise
Ventilation was measured during constant work rate exercise tests. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.
Measured: 4 weeks
Intensity of "Unpleasantness of Breathing" at Isotime Exercise
Intensity rating (modified 10-point Borg scale) measured at a standardized time (isotime) during constant work rate exercise tests. A rating of 0 represents no "unpleasantness of breathing" up to a maximum of 10. An improvement would be noted as a decrease in the Borg scale rating. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.
Measured: 4 weeks
Inspiratory Capacity at Isotime Exercise
Measurements of inspiratory capacity (IC) were conducted during constant work rate exercise tests. Isotime was defined as the highest time in minutes completed in both post-treatment tests.
Measured: 4 weeks
Diaphragm Electromyogram (EMGdi) at Isotime Exercise
EMGdi was measured during constant work rate exercise tests via a multipair-electrode esophageal catheter. EMGdi expressed as a percentage of its maximum is used as an index of inspiratory neural drive. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.
Measured: 4 weeks
Tidal Esophageal Pressure (Pes) Swings at Isotime Exercise
Tidal esophageal pressure (Pes) swings were measured via an esophageal balloon catheter during constant work rate exercise tests. Tidal Pes expressed relative to maximum is an index of respiratory effort. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.
Measured: 4 weeks
Mean Expiratory Flow at Isotime Exercise
Mean expiratory flow was measured during constant work rate exercise tests. Isotime was defined as the highest exercise time in minutes common to both post-treatment tests.
Measured: 4 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Measurements of pulmonary function included spirometry and body plethysmography. Values reported are 90 minutes post-dose after 4 weeks of treatment.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Dr. Denis O'Donnell, Queen's University
- Investigators
- Denis E O'Donnell, MD, FRCPC, Principal investigator, Queen's University and Kingston General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01491802
- Sponsor's protocol ID
- DMED-1426-11
- Status last verified
- May 2017
- First submitted
- 12 Dec 2011
- Last updated
- 15 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 4-week Randomized, Double-blind, Crossover Study to Assess the Effect of a New LABA/LAMA Combination Versus LAMA Alone on Exertional Dyspnea, Exercise Endurance and Neuromechanical Coupling in Patients With GOLD Stage II COPD
- ClinicalTrials.gov ID
- NCT01491802
- Acronym / sponsor ID
- DMED-1426-11
- Conditions
- COPD
- Keywords
- COPD, Combination therapy, Anticholinergic, Beta2-agonist, Exercise, Dyspnea, Respiratory mechanics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Queen's UniversityUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jan 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 14 Dec 2011 (estimated)
- Results
- Posted 15 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preliminary information from our laboratory indicated that even patients with milder chronic obstructive pulmonary disease (COPD) can have significant physiological derangements which become more pronounced during exercise, leading to intolerable dyspnea at lower levels of ventilation than in health. This study will explore pathophysiological mechanisms of dyspnea and activity limitation in GOLD stage II COPD and will determine if there is a sound physiological rationale for the use of dual long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) therapy (GSK573719/ GW642444 Inhalation Powder) versus LAMA alone (GSK573719) as treatment for dyspnea and exercise intolerance in this subpopulation. Objectives of this study are to determine if: 1) neuromechanical uncoupling of the respiratory system contributes to exertional dyspnea in milder COPD, and 2) treatment with LABA/LAMA improves dyspnea and exercise endurance compared with LAMA by improving neuromechanical coupling. The investigators hypothesize that: 1) dyspnea is related to excessive dynamic lung hyperinflation, tidal volume restriction and increased ratio of central respiratory neural drive to tidal volume displacement, a measure of neuromechanical uncoupling of the respiratory system, and 2) LABA/LAMA will improve dyspnea and exercise endurance, which will be explained by partial reversal of the above mechanical abnormalities. The investigators will conduct a randomized, double-blind crossover study and compare the effects of once-daily LABA/LAMA over 4-weeks with LAMA on dyspnea, exercise endurance and ventilatory mechanics in GOLD stage II COPD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LAMA alone, then LAMA/LABA combination | Experimental | Drug: LAMA/LABA, Drug: LAMAParticipants will first receive an inhaled long-acting muscarinic antagonist (LAMA) once daily for 4 weeks. After a 2 week washout period, they will then receive the fixed-dose combination product [LAMA plus long-acting beta2-agonist (LABA)] once daily for 4 weeks. |
| LABA/LAMA combination, then LAMA alone | Experimental | Drug: LAMA/LABA, Drug: LAMAParticipants will first receive a long-acting muscarinic antagonist (LAMA) plus long-acting beta2-agonist (LABA) combination product once daily for 4 weeks. After a 2 week washout period, they will then receive the LAMA single product once daily for 4 weeks. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Stable moderate COPD
- Post-bronchodilator FEV1/FVC<0.7 and 50%≤FEV1<80% predicted
- Baseline Dyspnea Index ≤ 9 and MRC dyspnea scale >2
- Cigarette smoking history at least 20 pack-years
Key exclusion criteria (4 listed)
- Presence of a significant disease other than COPD that could contribute to dyspnea and exercise limitation
- Important contraindications to clinical exercise testing
- Use of daytime oxygen
- History of asthma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAMA/LABAAlso: GSK573719+GW642444, umeclidinium (GSK573719) / vilanterol (GW642444), Anoro ELLIPTAGSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy will be taken once daily for 4 weeks. | Drug | LABA/LAMA combination, then LAMA alone, LAMA alone, then LAMA/LABA combination |
| LAMAAlso: umeclidiniumGSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks | Drug | LABA/LAMA combination, then LAMA alone, LAMA alone, then LAMA/LABA combination |
Primary outcome
Exertional Dyspnea Intensity at Isotime Exercise.
Time frame: 4 weeks
Intensity of dyspnea (defined as breathing discomfort) at a standardized time (isotime) during constant work rate exercise tests as measured by the modified 10-point Borg scale. A rating of 0 represents no dyspnea up to a maximum of 10: a smaller rating is therefore an improvement. Isotime was defined as the highest exercise time in minutes completed in both post-treatment tests.
9 secondary outcomes
Exercise Endurance Time
Time frame: 4 weeks
Inspiratory Capacity at Rest
Time frame: 4 weeks
Ventilation at Isotime Exercise
Time frame: 4 weeks
Intensity of "Unpleasantness of Breathing" at Isotime Exercise
Time frame: 4 weeks
Inspiratory Capacity at Isotime Exercise
Time frame: 4 weeks
Diaphragm Electromyogram (EMGdi) at Isotime Exercise
Time frame: 4 weeks
Tidal Esophageal Pressure (Pes) Swings at Isotime Exercise
Time frame: 4 weeks
Mean Expiratory Flow at Isotime Exercise
Time frame: 4 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denis E O'Donnell, MD, FRCPC principal investigator
Queen's University and Kingston General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LAMA/LABA and LAMA in people with COPD, run by Queen's University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exertional Dyspnea Intensity at Isotime Exercise. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2017.