Clinical trial NCT00157235: Effect of Tiotropium Inhalation Capsules (Spiriva) on Exercise Tolerance in COPD Patients
Official title: A Randomized, Double Blind , Placebo Controlled Trial to Compare the Effect of Tiotropium Inhalation Capsules on Exercise Tolerance in Patients With COPD Participating in 8 Weeks of Pulmonary Rehabilitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 234
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.. .

Eligibility 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 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.

Primary outcomes:
measure: Change in six minute walk distance after 8 weeks of pulmonary rehabilitation.
timeFrame: week 13
Secondary outcomes:
measure: Individual FEV1 measurement
timeFrame: week 4, 13, 25
measure: Individual FVC measurement
timeFrame: week 4, 13, 25
measure: St. George's Hospital Respiratory Questionnaire (SGRQ)
timeFrame: Time Frame: week 4, 13, 25
measure: Transition dyspnea index
timeFrame: week 4, 13, 25
measure: COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest
timeFrame: week 4, 13, 25
measure: Amount of salbutamol therapy used during the treatment period
timeFrame: 25 weeks
measure: Number and length of exacerbations of COPD
timeFrame: 25 weeks
measure: Physician's global evaluation
timeFrame: week 4, 13, 25
measure: Patient peak flow rates (PEFR) twice daily
timeFrame: 25 weeks
measure: Patient activity measurement
timeFrame: week 4, 9, 13, 17, 21, 25
measure: Six minute walk distance
timeFrame: week 13, 25
measure: Occurrence of adverse events
timeFrame: 25 weeks
measure: Changes from baseline in Pulse rate and blood pressure in conjunction with spirometry
timeFrame: 25 weeks
measure: Changes in the physical examination from baseline and at the conclusion of patient participation in the trial
timeFrame: 25 weeks
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Fondazione "S. Maugeri"
city: Casorate Primo (PV)
country: Italy
facility: Azienda Sanitaria Locale
city: Ferrara
country: Italy
facility: Arcispedale S. Anna
city: Genova
country: Italy
facility: U.O. dimedicina Preventiva del Lavoro
city: Gussago (BS)
country: Italy
facility: Fondazione Maugeri
city: Pisa
country: Italy
facility: Universita degli Studi di Pisa
city: Pozzolatico (FI)
country: Italy
facility: Fondazione Don Gnocchi
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Camillo Forlanini
city: Telese Terme (BN)
country: Italy
facility: Fondazione S. Maugeri
city: Tradate (VA)
country: Italy
facility: Fondazione "S. Maugeri"
city: Trieste
country: Italy
facility: Ospedali Riuniti di Trieste
city: Velletri (Roma)
country: Italy
facility: Casa di Cura San Raffaele
Study officials:
affiliation: BI Italy
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: