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Effect of Tiotropium Inhalation Capsules (Spiriva) on Exercise Tolerance in COPD Patients

Phase 3
Completed
Conditions
Pulmonary Disease, Chronic Obstructive
Registration Number
NCT00157235
Lead Sponsor
Boehringer Ingelheim
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.. .

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
234
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Change in six minute walk distance after 8 weeks of pulmonary rehabilitation.week 13
Secondary Outcome Measures
NameTimeMethod
Individual FVC measurementweek 4, 13, 25
Patient activity measurementweek 4, 9, 13, 17, 21, 25
Six minute walk distanceweek 13, 25
Changes from baseline in Pulse rate and blood pressure in conjunction with spirometry25 weeks
Individual FEV1 measurementweek 4, 13, 25
COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chestweek 4, 13, 25
St. George's Hospital Respiratory Questionnaire (SGRQ)Time Frame: week 4, 13, 25
Transition dyspnea indexweek 4, 13, 25
Amount of salbutamol therapy used during the treatment period25 weeks
Physician's global evaluationweek 4, 13, 25
Number and length of exacerbations of COPD25 weeks
Patient peak flow rates (PEFR) twice daily25 weeks
Occurrence of adverse events25 weeks
Changes in the physical examination from baseline and at the conclusion of patient participation in the trial25 weeks

Trial Locations

Locations (11)

Fondazione Don Gnocchi

🇮🇹

Pozzolatico (FI), Italy

Fondazione "S. Maugeri"

🇮🇹

Tradate (VA), Italy

Arcispedale S. Anna

🇮🇹

Ferrara, Italy

Universita degli Studi di Pisa

🇮🇹

Pisa, Italy

U.O. dimedicina Preventiva del Lavoro

🇮🇹

Genova, Italy

Azienda Sanitaria Locale

🇮🇹

Casorate Primo (PV), Italy

Fondazione Maugeri

🇮🇹

Gussago (BS), Italy

Fondazione S. Maugeri

🇮🇹

Telese Terme (BN), Italy

Ospedali Riuniti di Trieste

🇮🇹

Trieste, Italy

Azienda Ospedaliera S. Camillo Forlanini

🇮🇹

Roma, Italy

Casa di Cura San Raffaele

🇮🇹

Velletri (Roma), Italy

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