Investigate the Impact of Early Treatment Initiation With Tiotropium in Patients Recovering From Hospitalization for an Acute COPD Exacerbation 1
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ClinicalTrials.gov Identifier: NCT01663987 |
Recruitment Status
:
Completed
First Posted
: August 14, 2012
Results First Posted
: July 9, 2015
Last Update Posted
: July 9, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Pulmonary Disease, Chronic Obstructive | Drug: tiotropium bromide Drug: Placebo | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 79 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double |
Primary Purpose: | Treatment |
Official Title: | A Randomized, Placebo-controlled, Double-blind, Parallel Group, Multi Center Study to Assess the Safety and Efficacy of Tiotropium Bromide (18 µg) Delivered Via the HandiHaler® in Chronic Obstructive Pulmonary Disease (COPD) Subjects Recovering From Hospitalization for an Acute Exacerbation (Hospital Discharge Study 1) |
Study Start Date : | August 2012 |
Actual Primary Completion Date : | May 2014 |
Actual Study Completion Date : | May 2014 |

Arm | Intervention/treatment |
---|---|
Active Comparator: 18 mcg tiotropium
Patient to receive one tiotropium bromide inhalation powder capsule daily (in the morning) via HandiHaler
|
Drug: tiotropium bromide
18 mcg QD
|
Placebo Comparator: Placebo
Patient to receive one placebo capsule daily (in the morning) identical to those containing tiotropium bromide inhalation powder via HandiHaler
|
Drug: Placebo
QD
|
- Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug [ Time Frame: Baseline and 12 weeks ]Change from baseline in trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study medication. Trough FEV1 is defined as FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of drug.
- Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: From first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years ]
Percentage of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.
Time to the next adverse clinical outcome event from the two twin trials, was defined as a primary endpoint but was not analysed numerically, so this endpoint is presented instead.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Change From Baseline of Trough FVC at 12 Weeks on Study Drug [ Time Frame: Baseline and 12 weeks ]Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.
- Percentage of Patients With Adverse Clinical Event on Study [ Time Frame: From first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years ]Percentage of patients with adverse clinical event during on study, which is defined as the combined endpoint of chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalisation, or all cause mortality.
- Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: Baseline and 12 weeks ]
Change from baseline of Trough FEV1 (forced expiratory volume in one second) at 12 weeks on study drug.
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: Baseline and 12 weeks ]
Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years ]
Percentage of patients with COPD exacerbation on study was analysed for the combined study.
A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following: 1) Shortness of breath; 2) Sputum production (volume); 3)Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness. Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment.
A required change in treatment included either prescription of antibiotics and/or systemic steroids; and a newly prescribed maintenance respiratory medication (i.e. bronchodilators including theophyllines and PDE4-inhibitors).
This endpoint was analysed using combined data, as specified in the analysis plan.
- Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years ]
Percentage of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study.
All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures. Hospitalizations occurring on the same day as discharge were not considered a separate admission.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Percentage of Patients With 30-day Readmission Rates Outcome Event From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: from date of hospital discharge prior to randomization up to readmission days >1 and <31 days ]
Percentage of patients with 30-day hospital readmission rates outcome events was analysed.
Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1.
The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days >1 and <31 days using the TS.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: Start of treatment to the last timepoint with information of clinical adverse outcome available, up to 2 years ]
Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: From first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years ]
Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.
This endpoint was analysed using combined data, as specified in the analysis plan.
- Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986) [ Time Frame: From first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years ]
Time to event: Time to recovery (EXACT-PRO) was not analysed, only Kaplan meier curve was plotted. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2 and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average.
This endpoint was analysed using combined data, as specified in the analysis plan.

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Ages Eligible for Study: | 40 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion criteria:
The following inclusion criteria apply at Visit 0:
- All subjects must sign an informed consent consistent with the International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial and conducting any study procedures.
- Male or female subjects 40 years of age or older.
- Hospitalization for a primary diagnosis of acute COPD exacerbation for =14 days. Determination of accuracy of admission diagnosis will be at the discretion of the investigator.
-
Patient reported hospital length of stay and discharge date (confirmed with hospital discharge summary/hospital records; however, medical record confirmation may occur following randomization).
The following inclusion criteria apply at Visit 1:
- Discharged from the hospital =10 days from date of randomization.
- All subjects must have a diagnosis of COPD (P12-01205), and have documented airway obstruction with a post-bronchodilator FEV1/FVC <0.7(See Section 5.1.2, Pulmonary Function Testing). The diagnosis of COPD can be made at Visit 1 if no PFT data available within the past 12 months.
- Subjects must be current or ex-smoker with a smoking history of =10 pack-years:
Pack-years = Number of cigarettes/day x years of smoking 20 cigarettes/ pack 8. Subjects must be able to inhale medication in a competent manner from the HandiHaler® device (Appendix 10.1) and from a metered dose inhaler (MDI).
Exclusion criteria:
The following exclusion criterion applies at Visit 0:
-
No more than 30 days of therapy with any long-acting inhaled anticholinergic over preceding 3 months prior to discharge from the hospital, and no therapy with any long acting anticholinergic post discharge (no use between hospital discharge and randomization) or any other restricted concomitant medications
The following exclusion criteria apply at Visit 1:
- Presence of a significant disease (in the opinion of the investigator) which may put the subject at risk because of participation in the study or may influence the subject's ability to participate in the study for up to 2 years.
- A documented history of myocardial infarction during the hospitalization preceding randomization. Subjects being stable with a history of cardiac stents are permitted.
- Any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year.
- Subjects with asthma (subject treated for asthma in the last 2 years, history of childhood asthma is permitted), cystic fibrosis, clinical diagnosis of bronchiectasis, interstitial lung disease, pulmonary thromboembolic disease or known active tuberculosis.
7. Malignancy for which the subject has undergone resection, radiation, chemotherapy or biological treatments within the last two years or is currently on active radiation therapy, chemotherapy or biological treatment. Subjects with treated basal cell carcinoma and non-invasive squamous cell skin carcinoma are allowed.
8. Hospitalization for cardiac failure (New York Heart Association (NYHA) class III or IV) during the hospitalization preceding randomization.
9. Known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler® or MDI inhalation solution delivery system.
10. Known moderate to severe renal impairment as judged by the investigator. 11. Known narrow angle glaucoma as judged by the investigator. 12. Significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Subjects whose symptoms are controlled on treatment may be included. 13. 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 sub dermal implants e.g., Norplant) for at least three months prior to and for the duration of the trial.
14. Significant alcohol or drug abuse within the past 12 months. 15. Previously randomized in this study or currently participating in another interventional study.
16. Visual impairment that as judged by the investigator does not allow the subject to independently read and complete the questionnaires and eDiary.
17. Any significant or new ECG findings at Visit 1 as judged by the investigator, including, but not limited to signs of acute ischemia, arrhythmia.
18. Treatment with any restricted pulmonary medication. 19. Residing in an assisted living facility.

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 ClinicalTrials.gov identifier (NCT number): NCT01663987

United States, Alabama | |
205.477.001039 Boehringer Ingelheim Investigational Site | |
Birmingham, Alabama, United States | |
205.477.001050 Boehringer Ingelheim Investigational Site | |
Birmingham, Alabama, United States | |
205.477.001021 Boehringer Ingelheim Investigational Site | |
Florence, Alabama, United States | |
United States, California | |
205.477.001046 Boehringer Ingelheim Investigational Site | |
Fountain Valley, California, United States | |
205.477.001052 Boehringer Ingelheim Investigational Site | |
Sacramento, California, United States | |
205.477.001059 Boehringer Ingelheim Investigational Site | |
San Diego, California, United States | |
United States, Connecticut | |
205.477.001009 Boehringer Ingelheim Investigational Site | |
Stamford, Connecticut, United States | |
205.477.001040 Boehringer Ingelheim Investigational Site | |
Waterbury, Connecticut, United States | |
United States, Florida | |
205.477.001051 Boehringer Ingelheim Investigational Site | |
Brandon, Florida, United States | |
205.477.001044 Boehringer Ingelheim Investigational Site | |
Clearwater, Florida, United States | |
205.477.001037 Boehringer Ingelheim Investigational Site | |
Eustis, Florida, United States | |
205.477.001017 Boehringer Ingelheim Investigational Site | |
Miami, Florida, United States | |
205.477.001063 Boehringer Ingelheim Investigational Site | |
Miami, Florida, United States | |
205.477.001001 Boehringer Ingelheim Investigational Site | |
St. Petersburg, Florida, United States | |
United States, Georgia | |
205.477.001004 Boehringer Ingelheim Investigational Site | |
Decatur, Georgia, United States | |
205.477.001012 Boehringer Ingelheim Investigational Site | |
Duluth, Georgia, United States | |
United States, Illinois | |
205.477.001064 Boehringer Ingelheim Investigational Site | |
Belleville, Illinois, United States | |
United States, Indiana | |
205.477.001038 Boehringer Ingelheim Investigational Site | |
Muncie, Indiana, United States | |
United States, Maryland | |
205.477.001007 Boehringer Ingelheim Investigational Site | |
Baltimore, Maryland, United States | |
205.477.001014 Boehringer Ingelheim Investigational Site | |
Columbia, Maryland, United States | |
United States, Michigan | |
205.477.001018 Boehringer Ingelheim Investigational Site | |
Livonia, Michigan, United States | |
United States, New Jersey | |
205.477.001068 Boehringer Ingelheim Investigational Site | |
Union, New Jersey, United States | |
United States, New York | |
205.477.001035 Boehringer Ingelheim Investigational Site | |
Cooperstown, New York, United States | |
205.477.001023 Boehringer Ingelheim Investigational Site | |
New York, New York, United States | |
205.477.001061 Boehringer Ingelheim Investigational Site | |
Staten Island, New York, United States | |
United States, North Carolina | |
205.477.001027 Boehringer Ingelheim Investigational Site | |
Burlington, North Carolina, United States | |
205.477.001032 Boehringer Ingelheim Investigational Site | |
Huntersville, North Carolina, United States | |
205.477.001020 Boehringer Ingelheim Investigational Site | |
Seneca, North Carolina, United States | |
United States, Ohio | |
205.477.001034 Boehringer Ingelheim Investigational Site | |
Cincinnati, Ohio, United States | |
205.477.001053 Boehringer Ingelheim Investigational Site | |
Columbus, Ohio, United States | |
205.477.001011 Boehringer Ingelheim Investigational Site | |
Dayton, Ohio, United States | |
United States, Oklahoma | |
205.477.001057 Boehringer Ingelheim Investigational Site | |
Tulsa, Oklahoma, United States | |
United States, Oregon | |
205.477.001006 Boehringer Ingelheim Investigational Site | |
Portland, Oregon, United States | |
United States, Pennsylvania | |
205.477.001083 Boehringer Ingelheim Investigational Site | |
Downington, Pennsylvania, United States | |
205.477.001031 Boehringer Ingelheim Investigational Site | |
Monroeville, Pennsylvania, United States | |
United States, South Carolina | |
205.477.001028 Boehringer Ingelheim Investigational Site | |
Anderson, South Carolina, United States | |
205.477.001019 Boehringer Ingelheim Investigational Site | |
Charleston, South Carolina, United States | |
205.477.001010 Boehringer Ingelheim Investigational Site | |
Fort Mill, South Carolina, United States | |
205.477.001025 Boehringer Ingelheim Investigational Site | |
Gaffney, South Carolina, United States | |
205.477.001002 Boehringer Ingelheim Investigational Site | |
Rock Hill, South Carolina, United States | |
205.477.001026 Boehringer Ingelheim Investigational Site | |
Spartanburg, South Carolina, United States | |
205.477.001015 Boehringer Ingelheim Investigational Site | |
Union, South Carolina, United States | |
United States, Tennessee | |
205.477.001013 Boehringer Ingelheim Investigational Site | |
Nashville, Tennessee, United States | |
United States, Texas | |
205.477.001022 Boehringer Ingelheim Investigational Site | |
Corsicana, Texas, United States | |
205.477.001055 Boehringer Ingelheim Investigational Site | |
Fort Worth, Texas, United States | |
205.477.001054 Boehringer Ingelheim Investigational Site | |
Katy, Texas, United States | |
205.477.001062 Boehringer Ingelheim Investigational Site | |
Tyler, Texas, United States | |
United States, Virginia | |
205.477.001030 Boehringer Ingelheim Investigational Site | |
Abingdon, Virginia, United States | |
205.477.001008 Boehringer Ingelheim Investigational Site | |
Roanoke, Virginia, United States | |
Puerto Rico | |
205.477.001043 Boehringer Ingelheim Investigational Site | |
San Juan, Puerto Rico |
Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim |
Additional Information:
Responsible Party: | Boehringer Ingelheim |
ClinicalTrials.gov Identifier: | NCT01663987 History of Changes |
Other Study ID Numbers: |
205.477 |
First Posted: | August 14, 2012 Key Record Dates |
Results First Posted: | July 9, 2015 |
Last Update Posted: | July 9, 2015 |
Last Verified: | June 2015 |
Additional relevant MeSH terms:
Lung Diseases Pulmonary Disease, Chronic Obstructive Chronic Disease Respiratory Tract Diseases Lung Diseases, Obstructive Disease Attributes Pathologic Processes Tiotropium Bromide Bromides Bronchodilator Agents Autonomic Agents |
Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Parasympatholytics Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Anticonvulsants |