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.

Condition	Intervention	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Tiotropium bromide	Phase III

Further Study Details: 

Primary Outcomes: The primary endpoint is the change from baseline (Visit 2) in six minute walk distance after 8 weeks of pulmonary rehabilitation ( Visit 6).
Secondary Outcomes: Individual FEV1 and FVC measurements at each timepoint Saint George''''s Hospital Respiratory Questionnaire. Transition Dyspnea Index COPD symptom scores
Expected Total Enrollment:  220

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.. .

Ages Eligible for Study:  40 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

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 hospitalised for heart failure within the past three years.
• Patients with symptomatic benign prostatic hypertrophy or bladder neck bstruction.
• Patients with known narrow-angle glaucoma.

Please refer to this study by ClinicalTrials.gov identifier  NCT00157235

Patrizia LP Lessi, Dr.      +39 (02) 5355-280  Ext. 280    plessi@mil.boehringer-ingelheim.com

Italy
      Fondazione "S. Maugeri", Tradate (VA),  21049,  Italy; Completed
      Fondazione "S. Maugeri", Bari,  70020,  Italy; Recruiting
      Fondazione S. Maugeri, Telese Terme (BN),  82037,  Italy; Recruiting
      Azienda Sanitaria Locale, Casorate Primo (PV),  27022,  Italy; Recruiting
      Fondazione Maugeri, Gussago (BS),  25064,  Italy; Recruiting
      Università degli Studi di Pisa, Pisa,  56124,  Italy; Recruiting
      Azienda Ospedaliera S. Camillo Forlanini, Roma,  00149,  Italy; Recruiting
      Casa di Cura San Raffaele, Velletri (Roma),  00049,  Italy; Recruiting
      Ospedali Riuniti di Trieste, Trieste,  34100,  Italy; Recruiting
Italy, I
      Arcispedale S. Anna, Ferrara,  I,  44100,  Italy; Recruiting
      U.O. dimedicina Preventiva del Lavoro, Genova,  I,  16132,  Italy; Recruiting
      Fondazione Don Gnocchi, POZZOLATICO (FI),  I,  50020,  Italy; Recruiting

Study chairs or principal investigators

Patrizia LP Lessi, Dr.,  Study Chair,  BI Italy   

Study ID Numbers:  205.247
Last Updated:  September 10, 2005
Record first received:  September 7, 2005
ClinicalTrials.gov Identifier:  NCT00157235
Health Authority: Italy: Ministry of Health
ClinicalTrials.gov processed this record on 2005-09-13