Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The objective of this trial is to determine whether tiotropium inhalation capsules (Spiriva, Bromuro de Tiotropio), compared to placebo, enhances the improvement in exercise tolerance seen in patients with chronic obstructive pulmonary disease (COPD) who participate in pulmonary rehabilitation.
Detailed description
This is an 25-week multicenter, single country, randomised, double-blind, placebo-controlled, parallel group study to compare the efficacy of tiotropium inhalation capsules (Spiriva, Bromuro de Tiotropio) in patients with COPD participating in a pulmonary rehabilitation program. Following an initial screening, patients will perform a six minute walk test (Visit 1) and enter a 4-week run-in period. Patients will subsequently be randomized to tiotropium or placebo inhalation capsules taken once daily in the morning for the next 25 weeks. After successfully completing 4 weeks of study drug self-administration, patients will enter a period of pulmonary rehabilitation. Pulmonary rehabilitation will include aerobic lower limb exercise 3 times weekly for 8 weeks. After the last pulmonary rehabilitation session, patients will continue on study medication for a 12 week follow-up period. Six minute walk tests will be repeated during the run-in period at Week 0 (Visit 2) and Week 4 (Visit 3), at the conclusion of the 8 weeks of pulmonary rehabilitation (Visit 6) and the 12 weeks of follow-up (Visit 9). Pulmonary function testing will be conducted prior to the start of therapy at Visit 1 and at Visits 2 (week 0 ), 3 (week 4 ), 6 (week 13 ) and 9 (week 25 ). Study Hypothesis: The null hypothesis is that there is no difference in the increase in six minute walk distance between tiotropium and placebo groups following 8 weeks pulmonary rehabilitation program. The alternative hypothesis is that tiotropium with pulmonary rehabilitation increases six minute walk distance more than placebo with pulmonary rehabilitation. However, the two-sided test of hypothesis will be performed at 0.05 level of significance. Comparison(s): The primary endpoint is the six minute walk distance at visit 6. This endpoint will be compared between tiotropium and placebo using an analysis of covariance model with treatment, center and baseline (six-minute walk distance measured at visit 2 prior to dosing) as a covariate. Fifty-four meters has been determined to be the difference in six minute walk distance between tiotropium (Spiriva, Bromuro de Tiotropio) and placebo at 5% level of significance with at least 80% power using a two-tailed t-test.. .
Interventions
DRUGTiotropium bromide
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* COPD patients with FEV1 less 60% of predicted FEV1 less 70% of FVC.
Exclusion criteria
* Patients with any respiratory infection in the six weeks prior to the Screening Visit or during the run-in period (between Visits 1 and 2). * Patients with a recent history (i.e., 6 months - or less) of myocardial infarction. * Patients with any cardiac arrhythmia requiring drug therapy in the past year or who have been hospitalized for heart failure within the past three years. * Patients with symptomatic benign prostatic hypertrophy or bladder neck obstruction. * Patients with known narrow-angle glaucoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in six minute walk distance after 8 weeks of pulmonary rehabilitation. | week 13 |
Secondary
| Measure | Time frame |
|---|---|
| Individual FVC measurement | week 4, 13, 25 |
| St. George's Hospital Respiratory Questionnaire (SGRQ) | Time Frame: week 4, 13, 25 |
| Transition dyspnea index | week 4, 13, 25 |
| COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest | week 4, 13, 25 |
| Amount of salbutamol therapy used during the treatment period | 25 weeks |
| Number and length of exacerbations of COPD | 25 weeks |
| Individual FEV1 measurement | week 4, 13, 25 |
| Patient peak flow rates (PEFR) twice daily | 25 weeks |
| Patient activity measurement | week 4, 9, 13, 17, 21, 25 |
| Six minute walk distance | week 13, 25 |
| Occurrence of adverse events | 25 weeks |
| Changes from baseline in Pulse rate and blood pressure in conjunction with spirometry | 25 weeks |
| Changes in the physical examination from baseline and at the conclusion of patient participation in the trial | 25 weeks |
| Physician's global evaluation | week 4, 13, 25 |
Countries
Italy
Outcome results
None listed