Clinical trial NCT00680056: Add-on Effects of Tiotropium Over Formoterol in Exercise Tolerance on Chronic Obstructive Pulmonary Disease Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Chronic Bronchitis
Pulmonary Emphysema
Keywords: Pulmonary Disease, Chronic Obstructive
Tiotropium
Formoterol
Bronchodilator Agents
Exercise Tolerance
Randomized Controlled Trial [Publication Type]
COPD
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
First posted: 2008-05-19
Enrollment: 33
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change in Exercise Tolerance From Baseline at 2 Weeks
timeFrame: Baseline and after 2 weeks with each treatment
Secondary outcomes:
measure: Mean Score on the Transitional Dyspnea Index (TDI)
timeFrame: After 2 week of each treatment
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE)
Study officials:
affiliation: Federal University of São Paulo
name: J Alberto Neder, MD, phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berton DC, Reis M, Siqueira AC, Barroco AC, Takara LS, Bravo DM, Andreoni S, Neder JA. Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD. Respir Med. 2010 Sep;104(9):1288-96. doi: 10.1016/j.rmed.2010.05.017. Epub 2010 Jun 26.