Investigate the Impact of Early Treatment Initiation With Tiotropium in Patients Recovering From Hospitalization for an Acute COPD Exacerbation 1

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01663987
First received: August 9, 2012
Last updated: June 17, 2015
Last verified: June 2015
  Purpose
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 1)

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: tiotropium bromide
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Change From Baseline of Trough FVC at 12 Weeks on Study Drug [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 79
Study Start Date: August 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

The following inclusion criteria apply at Visit 0:

  1. 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.
  2. Male or female subjects 40 years of age or older.
  3. 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.
  4. 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:

  5. Discharged from the hospital =10 days from date of randomization.
  6. 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.
  7. 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:

  1. 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:

  2. 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.
  3. A documented history of myocardial infarction during the hospitalization preceding randomization. Subjects being stable with a history of cardiac stents are permitted.
  4. Any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year.
  5. 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663987

  Hide Study Locations
Locations
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
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01663987     History of Changes
Other Study ID Numbers: 205.477 
Study First Received: August 9, 2012
Results First Received: May 1, 2015
Last Updated: June 17, 2015
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 21, 2016