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

December 27, 2017 updated by: Boehringer Ingelheim

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

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.

Study Overview

Status

Completed

Conditions

Pulmonary Disease, Chronic Obstructive

Intervention / Treatment

Drug: Tiotropium bromide

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.. .

Study Type

Interventional

Enrollment

234

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: RANDOMIZED
Interventional Model: PARALLEL
Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in six minute walk distance after 8 weeks of pulmonary rehabilitation. Time Frame: week 13	week 13

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2002

Primary Completion (ACTUAL)

April 1, 2006

Study Completion (ACTUAL)