Clinical trial NCT02172391: Effect of Tiotropium on Airway Diameter in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: The Effects of Tiotropium Therapy on Airway Diameter in Patients With COPD (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: 2014-06-24
Enrollment: 81
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: Trial to investigate the acute and chronic effect of tiotropium therapy on airway diameter in COPD patients as measured by inspiratory capacity (IC).


Eligibility criteria: Inclusion Criteria:

* All patients must have a diagnosis of chronic obstructive pulmonary disease
* Male or female patients ≥ 40 years of age but ≤ 75 years old
* Patients must have a smoking history of more than ten pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year
* Patients must be able to perform all specified procedures and maintain records during the study period as required in the protocol
* Patients must be able to inhale medication from the HandiHaler®
* All patients must sign a Patient Informed Consent Form prior to participation in the trial i.e., prior to pre-study washout of their usual pulmonary medications
* Patients must be willing to attend an outpatient clinic on a regular basis
* Patients must be able to walk 164 feet (50 meters) during the Six Minute Walk Test

Exclusion Criteria:

* Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
* Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis test results, if the abnormality defines a disease listed as an exclusion criterion
* Patients with a serum glutamic-oxaloacetic transaminase (SGOT) ≥1.5 x Upper Limit of Normal Range (ULN), serum glutamic-pyruvic transaminase (SGPT) ≥1.5 x ULN, bilirubin ≥1.5 x ULN or creatinine ≥ 1.5 x ULN regardless of the clinical condition
* Patients with a recent history (i.e., one year or less) of myocardial infarction
* Patients with a recent history (i.e., three years or less) of heart failure, pulmonary edema or patients with any cardiac arrhythmia (with or without symptoms)
* Patients with regular use of daytime oxygen therapy
* Patients with known active tuberculosis
* Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed
* Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis
* Patients who have undergone thoracotomy with pulmonary resection. Patients with a history or a thoracotomy for other reason should be evaluated as per exclusion criterion no. 1
* Patients with upper respiratory tract infection in the past six weeks prior to the Screening Visit or during the baseline period
* Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system
* Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
* Patients with known narrow-angle glaucoma
* Patients who are being treated with cromolyn sodium or nedocromil sodium
* Patients who are being treated with antihistamines (H1 receptor antagonists) or antileukotrienes and are not able to stop these medications 1 month before visit 1
* Patients using oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day
* Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
* Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥ 600/mm3
* Patients with history of (past five years or less) and/or active alcohol or drug abuse
* Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Period (Visit 1)
* Patients who have participated in any pulmonary rehabilitation program for COPD within 6 weeks prior to Visit 1 or throughout the study
* Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea such as arthritis in the leg, angina or claudication

Primary outcomes:
measure: Area under the curve from time 0 to 3 hours (AUC0-3) of resting inspiratory capacity (IC)
timeFrame: Day 28
measure: Trough resting IC
timeFrame: Day 28
Secondary outcomes:
measure: FEV1 (Forced expiratory volume in one second)
timeFrame: Day 1, 14 and 28
measure: FVC (forced vital capacity)
timeFrame: Day 1, 14 and 28
measure: FEF25%-75% (Forced Expiratory Flow, mid expiratory phase)
timeFrame: Day 1, 14 and 28
measure: FEF50% (Forced Expiratory Flow, at 50% of FVC)
timeFrame: Day 1, 14 and 28
measure: FEF75% (Forced Expiratory Flow, at 75% of FVC)
timeFrame: Day 1, 14, 28
measure: SVC (Slow vital capacity)
timeFrame: Day 1, 14, 28
measure: Respiratory System Transfer Impedance (Respiratory Resistance)
timeFrame: Day 1, 14 and 28
measure: Airway Resistance (Raw)
timeFrame: Day 1, 14 and 28
measure: Thoracic Gas Volume (TGV)
timeFrame: Day 1, 14 and 28
measure: Specific Airway Conductance (SGaw)
timeFrame: Day 1, 14 and 28
measure: Physician's Global Evaluation
timeFrame: Day 1 and 28
measure: Oxygen Saturation (SaO2) prior to six minute walk test
timeFrame: Day 1 and 28
measure: Oxygen Saturation (SaO2) post six minute walk test
timeFrame: Day 1 and 28
measure: IC prior to six minute walk test
timeFrame: Day 1 and 28
measure: IC post six minute walk test
timeFrame: Day 1 and 28
measure: Chronic Respiratory Questionnaire (CRQ)
timeFrame: Day 1 and 28
measure: Baseline Dyspnea Index (BDI)
timeFrame: Day 1
measure: Transition Dyspnea Index (TDI)
timeFrame: Day 28
measure: Change from baseline in seated blood pressure
timeFrame: Baseline, Day 1, 14 and 28
measure: Change from baseline in pulse rate
timeFrame: Baseline, Day 1, 14 and 28
measure: Occurrence of Adverse Events
timeFrame: until day 35
Other outcomes:
Locations:
Study officials:
References: