Clinical trial NCT00274508: Effect of Tiotropium (Spiriva) on Exercise Tolerance in COPD Patients
Official title: Effect of Tiotropium on Exercise Tolerance and Static and Dynamic Lung Volumes in COPD Patients (A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-11
Enrollment: 261
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate whether tiotropium (Spiriva) improves exercise endurance in patients with COPD


Eligibility criteria: Inclusion criteria:

Male or female patients with a clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) based on American Thoracic Society (ATS) guidelines with:

* Relatively stable, moderate to severe airway obstruction with an Forced Expiratory Volume in One Second (FEV1) less than or equal to 65% of predicted normal (determined at Visit 1).
* Presence of lung hyperinflation as demonstrated by Functional Residual Capacity determined by body plethysmography (TGV(FRC)) greater than or equal to 120% of predicted normal (determined at Visit 1).
* Age greater or equal to 40 years and less than or equal to 75 years.
* A cigarette smoking history of more than ten pack-years. A pack-year was defined as the equivalent of smoking one pack of cigarettes per day for a year.
* Able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
* Able to inhale the trial medication from the HandiHaler device.

Exclusion criteria:

* Patients with a significant disease other than COPD. A significant disease was defined as a disease which, in the opinion of the investigator, may have put the patient at risk because of participation in the trial or may have influenced the results of the trial or the patient's ability to participate in the trial.
* Patients with clinically significant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defined a disease listed as an exclusion criterion, the patient was excluded.
* Patients with Serum Glutamic Oxaloacetic Transaminase (SGOT) ≥1.5 x ULN (upper limit of normal range), Serum Glutamic Pyruvic Transaminase (SGPT) ≥1.5 x ULN bilirubin ≥1.5 x ULN or creatinine ≥1.5 x ULN were excluded regardless of the clinical condition.
* Patients with a recent history (i.e., 1 year or less) of myocardial infarction.
* Patients with a recent history (i.e., 3 years or less) of heart failure, pulmonary edema, or patients with cardiac arrhythmia (with or without symptoms) or any contraindication to exercise.
* Patients requiring the regular use of daytime oxygen therapy.
* Patients with known active tuberculosis.
* Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma were eligible.
* Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
* Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons were evaluated as per the first exclusion criterion (i.e., significant disease other than COPD).
* Patients with an upper respiratory tract infection in the 6 weeks prior to the Screening Visit (Visit 1) or during the run-in period.
* Further exclusion criteria apply.

Primary outcomes:
measure: Endurance time during a constant work rate exercise test to symptom limitation
timeFrame: 2 hours and 15 minutes after trial medication administration on Day 42
Secondary outcomes:
measure: Constant work rate exercise test to symptom limitation
timeFrame: 8 hours post-dose after 6 weeks of treatment
measure: Breathing discomfort during constant work rate exercise test as measured by the modified Borg Scale
timeFrame: 6 weeks
measure: Dynamic lung hyperinflation during exercise as determined by IRVdyn (IC minus VT) and EELVdyn (TLC)
timeFrame: 6 weeks
measure: Evaluation of VE and VEcap during exercise (selected centers)
timeFrame: 6 weeks
measure: Evaluation of static lung hyperinflation as measured by RV/TLC and by TGV(FRC)/TLC
timeFrame: 6 weeks
measure: Evaluation of TAC (TAV = TLC(BOX)-VA(IG))
timeFrame: 6 weeks
measure: Evaluation of slow vital capacity (SVC)
timeFrame: 6 weeks
measure: Evaluation of maximal expiratory flow rates and volumes FEV1, FVC, FEF25-75%, FEF50%, FEF75%, SVC
timeFrame: 6 weeks
measure: Evaluation of TGV, Raw, SGaw and RV
timeFrame: 6 weeks
measure: Evaluation of SaO2, VO2, VCO2, Ti, Te, VE, VT, breathing frequency (f) during constant work rate exercise test
timeFrame: 6 weeks
measure: Physician's Global Assessment
timeFrame: 6 weeks
measure: Assessement of Pulse/heart rate and blood pressure in conjunction with spirometry and exercise
timeFrame: 6 weeks
measure: Changes in Physical examination and ECG
timeFrame: 6 weeks
measure: Occurrence of Adverse Events
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: St. Elizabeth's Medical Center of Boston
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Nashville
country: United States
facility: St. Thomas Health Services
state: Tennessee
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas
state: Texas
city: Randwick
country: Australia
facility: Phase I Unit
state: New South Wales
city: Westmead
country: Australia
facility: Immunology Department
state: New South Wales
city: Daw Park
country: Australia
facility: Department of Respiratory Medicine
state: South Australia
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Department of Respiratory Medicine
state: Victoria
city: Calgary
country: Canada
facility: Respiratory Research
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Respiratory Clinic
state: British Columbia
city: Halifax
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Cardio Repiratory
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: 1053 Carling Avenue
state: Ontario
city: Toronto
country: Canada
facility: Department of Respiratory Medicine
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Chest Institute - McGill University Health Centre
state: Quebec
city: Montreal
country: Canada
facility: Pulmonary Function Lab
state: Quebec
city: Ste-Foy
country: Canada
facility: Hopital Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Hamburg
country: Germany
facility: Pneumologisches Forschungsinstitut GmbH am Krankenhaus
city: Hannover
country: Germany
facility: Fraunhofer-Institut für Toxikologie und
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln
city: Magdeburg
country: Germany
facility: Neurologische Klinik der Otto-von-Guericke-Universität
city: München
country: Germany
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: