Add-on Effects of Tiotropium Over Formoterol in Exercise Tolerance on Chronic Obstructive Pulmonary Disease Patients

Federal University of São Paulo33 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Pulmonary Disease, Chronic Obstructive Chronic Bronchitis

Interventions

Formoterol plus Placebo (Tiotropium)DRUG

Formoterol 12mcg-capsules (2x/d) + Placebo (Tiotropium) (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks.

Formoterol plus TiotropiumDRUG

Formoterol 12mcg-capsule (2x/dia) + Tiotropium 18mcg-capsule (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks.

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Percentage Change in Exercise Tolerance From Baseline at 2 Weeks

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)

Time frame: Baseline and after 2 weeks with each treatment

Secondary Outcomes

Mean Score on the Transitional Dyspnea Index (TDI)

TDI is a multidimensional clinical instrument developed to provide a comprehensive assessment of change in dyspnea after an intervention, considering three components (functional impairment, magnitude of task, and magnitude of effort). It ranges from -9 (major deterioration) to +9 (major improvement).

Time frame: After 2 week of each treatment