Randomised Cross-over Study to Compare the Effect of Formoterol Plus Tiotropium Versus Formoterol Monotherapy on Breathlessness, Dynamic Hyperinflation and Exercise Tolerance in Moderate-to-severe Stable COPD Patients
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Percentage Change in Exercise Tolerance From Baseline at 2 Weeks
Study Overview
Brief Summary
The primary objective is to comparatively evaluate the isolated effects of a long-acting beta2-adrenergic (formoterol fumarate 12µg b.i.d. via Aeroliser) and combined with a long-acting anti-cholinergic (tiotropium bromide 18µg o.d via Handihaler) on breathlessness, dynamic hyperinflation and exercise tolerance in patients with advanced, but stable, chronic obstructive pulmonary disease. The study hypothesis is that combining long acting bronchodilators with different action mechanisms would promote synergistic effects on clinical outcomes.
Detailed Description
This will be a single center, randomized, double-blind study consisting of two 2-week treatment periods separated by a 5-7 days washout phase without long-acting bronchodilators. Eligible patients who complete the one week screening phase will be randomized to one of two treatment sequences: 1) Formoterol --> Formoterol + Tiotropium or 2) Formoterol + Tiotropium --> Formoterol. During the treatment periods, patients will be allowed to use a short-acting beta2-adrenergic+short-acting anticholinergic as rescue medication (salbutamol+ipratropium via MDI)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •COPD patients aged ≥ 40 years with stable moderate-to-severe airflow obstruction (FEV1 < 70% and FEV1/FVC ≤ 70% of predicted normal value) post-bronchodilator
- •presenting with a long history of smoking (> 20 pack-years) and chronic breathlessness (Baseline Dyspnoea Index total score < 9)
Exclusion Criteria
- •significant cardiovascular disease, hospitalization for COPD exacerbation or presence of a respiratory tract infection within 1 month of screening
- •current or childhood asthma
- •a history of allergic rhinitis or other atopic disease
- •inability to interrupt usual bronchodilator medication
- •use of oral steroids within a month before screening
- •need for long-term oxygen therapy, arterial oxygen saturation < 85% at rest anemia, hypo- and hyperthyroidism, hyperadrenergic state
- •uncontrolled insulin dependent diabetes mellitus, malignancy, or any disease or condition which limits exercise performance other than COPD
- •change in inhaled corticosteroid or theophylline use within 1 month prior to screening
Arms & Interventions
1
Formoterol plus Placebo (Tiotropium)
Intervention: Formoterol plus Placebo (Tiotropium) (Drug)
2
Formoterol plus Tiotropium
Intervention: Formoterol plus Tiotropium (Drug)
Outcomes
Primary Outcomes
Percentage Change in Exercise Tolerance From Baseline at 2 Weeks
Time Frame: Baseline and after 2 weeks with each treatment
Percentage change from baseline in time to the limit of tolerance on a high intensity constant-speed treadmill exercise test (with a speed corresponding to 80% of that obtained during incremental test)
Secondary Outcomes
- Mean Score on the Transitional Dyspnea Index (TDI)(After 2 week of each treatment)