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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00157235
Recruitment Status : Completed
First Posted : September 12, 2005
Last Update Posted : December 28, 2017
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: Tiotropium bromide Phase 3

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.


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.. .

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Study Type : Interventional  (Clinical Trial)
Enrollment : 234 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
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 Start Date : September 2002
Actual Primary Completion Date : April 2006
Actual Study Completion Date : April 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Change in six minute walk distance after 8 weeks of pulmonary rehabilitation. [ Time Frame: week 13 ]

Secondary Outcome Measures :
  1. Individual FEV1 measurement [ Time Frame: week 4, 13, 25 ]
  2. Individual FVC measurement [ Time Frame: week 4, 13, 25 ]
  3. St. George's Hospital Respiratory Questionnaire (SGRQ) [ Time Frame: Time Frame: week 4, 13, 25 ]
  4. Transition dyspnea index [ Time Frame: week 4, 13, 25 ]
  5. COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest [ Time Frame: week 4, 13, 25 ]
  6. Amount of salbutamol therapy used during the treatment period [ Time Frame: 25 weeks ]
  7. Number and length of exacerbations of COPD [ Time Frame: 25 weeks ]
  8. Physician's global evaluation [ Time Frame: week 4, 13, 25 ]
  9. Patient peak flow rates (PEFR) twice daily [ Time Frame: 25 weeks ]
  10. Patient activity measurement [ Time Frame: week 4, 9, 13, 17, 21, 25 ]
  11. Six minute walk distance [ Time Frame: week 13, 25 ]
  12. Occurrence of adverse events [ Time Frame: 25 weeks ]
  13. Changes from baseline in Pulse rate and blood pressure in conjunction with spirometry [ Time Frame: 25 weeks ]
  14. Changes in the physical examination from baseline and at the conclusion of patient participation in the trial [ Time Frame: 25 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00157235

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Fondazione "S. Maugeri"
Bari, Italy, 70020
Azienda Sanitaria Locale
Casorate Primo (PV), Italy, 27022
Arcispedale S. Anna
Ferrara, Italy, 44100
U.O. dimedicina Preventiva del Lavoro
Genova, Italy, 16132
Fondazione Maugeri
Gussago (BS), Italy, 25064
Universita degli Studi di Pisa
Pisa, Italy, 56124
Fondazione Don Gnocchi
Pozzolatico (FI), Italy, 50020
Azienda Ospedaliera S. Camillo Forlanini
Roma, Italy, 00149
Fondazione S. Maugeri
Telese Terme (BN), Italy, 82037
Fondazione "S. Maugeri"
Tradate (VA), Italy, 21049
Ospedali Riuniti di Trieste
Trieste, Italy, 34100
Casa di Cura San Raffaele
Velletri (Roma), Italy, 00049
Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Study Coordinator BI Italy
Additional Information:
Layout table for additonal information Identifier: NCT00157235    
Other Study ID Numbers: 205.247
First Posted: September 12, 2005    Key Record Dates
Last Update Posted: December 28, 2017
Last Verified: December 2017
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Tiotropium Bromide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action