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The aim of the study is to investigate whether the early introduction of maintenance bronchodilator therapy during an acute symptomatic episode of the disease shows benefits on the recovery of symptoms. It also represents an opportunity to identify COPD patients earlier in their disease state and start maintenance therapy, if appropriate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tiotropium 18mcg | Experimental | active |
|
| Placebo | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tiotropium | Drug | 18mcg |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Trough FEV1 After 12 Weeks on Study Drug | The primary endpoint was trough forced expiratory volume in 1 second (FEV1) after 12 weeks on study drug. Trough forced expiratory volume in 1 second (FEV1)was defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Recovery From Acute Respiratory Symptoms | Time to recovery was assessed with the EXACT-PRO questionnaire tool. The EXACT-PRO was designed to collect data to quantify frequency, severity, and duration of exacerbations in patients with COPD including the onset of and the recovery from COPD exacerbations. The EXACT-PRO is a 14-item questionnaire. Each attribute or item was assessed on a five- or six-point ordinal scale and summed to yield a total score that was converted to a 0-100 scale, with higher scores indicating a more severe health state or exacerbation. The EXACT-PRO was answered by the patients on a daily basis in the evening. |
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Inclusion criteria:
Exclusion criteria:
Therapy with any long-acting bronchodilator, short-acting anticholinergic, inhaled corticosteroid or regular maintenance use (>14 consecutive days) of systemic corticosteroid (the latter for respiratory indications) during the previous 6 months (short course of systemic corticosteroid for up to 14 days for respiratory indications allowed); in case of use of systemic corticosteroid medication for other than respiratory conditions, then exclusion of unstable doses (i.e., less than six weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone-equivalent per day. In addition, daily use of short-acting beta2-agonist for more than a week prior to Visit 0 not allowed.
The following exclusion criteria apply at Visit 1:
Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence the patient¿s ability to participate in the study.
A recent history (i.e., six months or less) of myocardial infarction. Patients being stable with a history of cardiac stents prior to six month are permitted.
Any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year.
Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or IV) during the past year.
Any significant or new ECG findings at V1 as judged by the investigator, including, but not limited to signs of ischemia, arrhythmia, heart failure, or the report of chest pain.
Known active tuberculosis.
Current asthma (patient treated for asthma in the last 2 years), cystic fibrosis, clinical diagnosis of bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease.
A history of thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 2.
Malignancy for which the patient has undergone resection, radiation, chemotherapy or biological treatments within the last year or is currently on active radiation therapy, chemotherapy or biological treatment. Patients with treated basal cell carcinoma are allowed.
At visit 0 or 1, a severe respiratory infection, e.g. pneumonia (as suspected by investigator), any condition or exacerbation requiring ER visit or hospitalization, need for oxygen treatment.
Known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler® or MDI inhalation solution delivery system.
Treatment with any restricted pulmonary medication
Requirement of supplemental oxygen therapy for = 24 hours during the previous 6 months.
Known moderate to severe renal impairment.
Known narrow angle glaucoma.
Significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included.
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm or subdermal implants e.g., Norplant®) for at least three months prior to and for the duration of the trial.
Significant alcohol or drug abuse within the past 12 months.
Actively participating in a pulmonary rehabilitation program.
Previously randomized in this study or currently participating in another interventional study.
Visual impairment that as judged by the investigator does not allow the patient to independently read and complete the questionnaires and electronic diary (eDiary).
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 205.479.01017 Boehringer Ingelheim Investigational Site | Tucson | Arizona | United States | |||
| 205.479.01036 Boehringer Ingelheim Investigational Site |
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In this 12-week, randomised, double-blind, placebo-controlled, parallel group, multi-center Phase IV trial in chronic obstructive pulmonary disease (COPD), 140 patients were randomised to either Tiotropium 18 mcg or Placebo. Sixty eight (68) patients received Tiotropium 18 mcg and seventy two (72) patients received Placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | placebo - Placebo Inhalation capsule, HandiHaler® |
| FG001 | Tiotropium 18 mcg | active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler® |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
placebo |
|
| 12 weeks |
| Trough FVC (in Litres) at 12 Weeks | The trough Forced Vital Capacity (FVC) was defined as the FVC measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug. | 12 weeks |
| Responder Status at Week 4 Clinic Visit | Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented:
| 4 weeks |
| Responder Status at Week 12 Clinic Visit | Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented:
| 12 weeks |
| Weekly Rescue Medication Use Over the 12 Weeks of Study | Daily rescue albuterol use was recorded in the diary in response to the following question: How many puffs of rescue medication did you use during the last 24 hours? The weekly rescue medication use was derived by summing the daily uses over the 12 weeks and dividing this total by 12 weeks. | 12 weeks |
| Riverside |
| California |
| United States |
| 205.479.01024 Boehringer Ingelheim Investigational Site | San Diego | California | United States |
| 205.479.01043 Boehringer Ingelheim Investigational Site | DeLand | Florida | United States |
| 205.479.01040 Boehringer Ingelheim Investigational Site | St. Petersburg | Florida | United States |
| 205.479.01022 Boehringer Ingelheim Investigational Site | Chelsea | Michigan | United States |
| 205.479.01041 Boehringer Ingelheim Investigational Site | Picayune | Mississippi | United States |
| 205.479.01037 Boehringer Ingelheim Investigational Site | St Louis | Missouri | United States |
| 205.479.01005 Boehringer Ingelheim Investigational Site | Tabor City | North Carolina | United States |
| 205.479.01008 Boehringer Ingelheim Investigational Site | Wilmington | North Carolina | United States |
| 205.479.01003 Boehringer Ingelheim Investigational Site | Cincinnati | Ohio | United States |
| 205.479.01002 Boehringer Ingelheim Investigational Site | Pittsburgh | Pennsylvania | United States |
| 205.479.01044 Boehringer Ingelheim Investigational Site | Tipton | Pennsylvania | United States |
| 205.479.01006 Boehringer Ingelheim Investigational Site | Charleston | South Carolina | United States |
| 205.479.01001 Boehringer Ingelheim Investigational Site | Columbia | South Carolina | United States |
| 205.479.01007 Boehringer Ingelheim Investigational Site | Easley | South Carolina | United States |
| 205.479.01026 Boehringer Ingelheim Investigational Site | Fort Mill | South Carolina | United States |
| 205.479.01031 Boehringer Ingelheim Investigational Site | Gaffney | South Carolina | United States |
| 205.479.01012 Boehringer Ingelheim Investigational Site | Greenville | South Carolina | United States |
| 205.479.01048 Boehringer Ingelheim Investigational Site | Hodges | South Carolina | United States |
| 205.479.01004 Boehringer Ingelheim Investigational Site | Spartanburg | South Carolina | United States |
| 205.479.01019 Boehringer Ingelheim Investigational Site | Union | South Carolina | United States |
| 205.479.01039 Boehringer Ingelheim Investigational Site | Rapid City | South Dakota | United States |
| 205.479.01033 Boehringer Ingelheim Investigational Site | Chattanooga | Tennessee | United States |
| 205.479.01028 Boehringer Ingelheim Investigational Site | Killeen | Texas | United States |
| 205.479.01038 Boehringer Ingelheim Investigational Site | Ettrick | Virginia | United States |
| 205.479.01047 Boehringer Ingelheim Investigational Site | Norfolk | Virginia | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | placebo - Placebo Inhalation capsule, HandiHaler® |
| BG001 | Tiotropium 18mcg | active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler® |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Trough forced expiratory value (FEV1) | Mean | Standard Deviation | Litre |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Trough FEV1 After 12 Weeks on Study Drug | The primary endpoint was trough forced expiratory volume in 1 second (FEV1) after 12 weeks on study drug. Trough forced expiratory volume in 1 second (FEV1)was defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug. | Treated Set (TS) with non missing FEV1 data. | Posted | Least Squares Mean | Standard Error | Litre | 12 weeks |
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| Secondary | Time to Recovery From Acute Respiratory Symptoms | Time to recovery was assessed with the EXACT-PRO questionnaire tool. The EXACT-PRO was designed to collect data to quantify frequency, severity, and duration of exacerbations in patients with COPD including the onset of and the recovery from COPD exacerbations. The EXACT-PRO is a 14-item questionnaire. Each attribute or item was assessed on a five- or six-point ordinal scale and summed to yield a total score that was converted to a 0-100 scale, with higher scores indicating a more severe health state or exacerbation. The EXACT-PRO was answered by the patients on a daily basis in the evening. | TS with non missing EXACT-PRO data. | Posted | Geometric Mean | Standard Deviation | units on a scale | 12 weeks |
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| Secondary | Trough FVC (in Litres) at 12 Weeks | The trough Forced Vital Capacity (FVC) was defined as the FVC measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of study drug. | TS with non missing FVC data. | Posted | Least Squares Mean | Standard Deviation | Litres | 12 weeks |
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| Secondary | Responder Status at Week 4 Clinic Visit | Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented:
| Responder defined by >= 20% improvement. TS with non missing responder data. | Posted | Number | participants | 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Responder Status at Week 12 Clinic Visit | Responder status was determined at each clinic visit. The number and percentage of subjects in each of the following 3 classes were presented:
| TS with non missing responder data at week 12. Responder defined by >= 20% improvement. . | Posted | Number | participants | 12 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Weekly Rescue Medication Use Over the 12 Weeks of Study | Daily rescue albuterol use was recorded in the diary in response to the following question: How many puffs of rescue medication did you use during the last 24 hours? The weekly rescue medication use was derived by summing the daily uses over the 12 weeks and dividing this total by 12 weeks. | TS with non missing rescue medication use. | Posted | Mean | Standard Deviation | puffs | 12 weeks |
|
|
12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | placebo - Placebo Inhalation capsule, HandiHaler® | 3 | 72 | 8 | 72 | ||
| EG001 | Tiotropium 18 mcg | active - Tiotropium bromide Inhalation capsule 18 mcg, HandiHaler® | 3 | 68 | 6 | 68 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | MEDDRA 16.0 | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MEDDRA 16.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MEDDRA 16.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MEDDRA 16.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MEDDRA 16.0 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MEDDRA 16.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.0 | Systematic Assessment |
|
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
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| >=65 years |
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| Male |
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