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

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)

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)

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: tiotropium bromide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico
    • 205.477.001043 Boehringer Ingelheim Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • 205.477.001039 Boehringer Ingelheim Investigational Site
    • Birmingham, Alabama, United States
      • 205.477.001050 Boehringer Ingelheim Investigational Site
    • Florence, Alabama, United States
      • 205.477.001021 Boehringer Ingelheim Investigational Site
  • California
    • Fountain Valley, California, United States
      • 205.477.001046 Boehringer Ingelheim Investigational Site
    • Sacramento, California, United States
      • 205.477.001052 Boehringer Ingelheim Investigational Site
    • San Diego, California, United States
      • 205.477.001059 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Stamford, Connecticut, United States
      • 205.477.001009 Boehringer Ingelheim Investigational Site
    • Waterbury, Connecticut, United States
      • 205.477.001040 Boehringer Ingelheim Investigational Site
  • Florida
    • Brandon, Florida, United States
      • 205.477.001051 Boehringer Ingelheim Investigational Site
    • Clearwater, Florida, United States
      • 205.477.001044 Boehringer Ingelheim Investigational Site
    • Eustis, Florida, United States
      • 205.477.001037 Boehringer Ingelheim Investigational Site
    • Miami, Florida, United States
      • 205.477.001017 Boehringer Ingelheim Investigational Site
    • Miami, Florida, United States
      • 205.477.001063 Boehringer Ingelheim Investigational Site
    • Saint Petersburg, Florida, United States
      • 205.477.001001 Boehringer Ingelheim Investigational Site
  • Georgia
    • Decatur, Georgia, United States
      • 205.477.001004 Boehringer Ingelheim Investigational Site
    • Duluth, Georgia, United States
      • 205.477.001012 Boehringer Ingelheim Investigational Site
  • Illinois
    • Belleville, Illinois, United States
      • 205.477.001064 Boehringer Ingelheim Investigational Site
  • Indiana
    • Muncie, Indiana, United States
      • 205.477.001038 Boehringer Ingelheim Investigational Site
  • Maryland
    • Baltimore, Maryland, United States
      • 205.477.001007 Boehringer Ingelheim Investigational Site
    • Columbia, Maryland, United States
      • 205.477.001014 Boehringer Ingelheim Investigational Site
  • Michigan
    • Livonia, Michigan, United States
      • 205.477.001018 Boehringer Ingelheim Investigational Site
  • New Jersey
    • Union, New Jersey, United States
      • 205.477.001068 Boehringer Ingelheim Investigational Site
  • New York
    • Cooperstown, New York, United States
      • 205.477.001035 Boehringer Ingelheim Investigational Site
    • New York, New York, United States
      • 205.477.001023 Boehringer Ingelheim Investigational Site
    • Staten Island, New York, United States
      • 205.477.001061 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Burlington, North Carolina, United States
      • 205.477.001027 Boehringer Ingelheim Investigational Site
    • Huntersville, North Carolina, United States
      • 205.477.001032 Boehringer Ingelheim Investigational Site
    • Seneca, North Carolina, United States
      • 205.477.001020 Boehringer Ingelheim Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • 205.477.001034 Boehringer Ingelheim Investigational Site
    • Columbus, Ohio, United States
      • 205.477.001053 Boehringer Ingelheim Investigational Site
    • Dayton, Ohio, United States
      • 205.477.001011 Boehringer Ingelheim Investigational Site
  • Oklahoma
    • Tulsa, Oklahoma, United States
      • 205.477.001057 Boehringer Ingelheim Investigational Site
  • Oregon
    • Portland, Oregon, United States
      • 205.477.001006 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Downingtown, Pennsylvania, United States
      • 205.477.001083 Boehringer Ingelheim Investigational Site
    • Monroeville, Pennsylvania, United States
      • 205.477.001031 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Anderson, South Carolina, United States
      • 205.477.001028 Boehringer Ingelheim Investigational Site
    • Charleston, South Carolina, United States
      • 205.477.001019 Boehringer Ingelheim Investigational Site
    • Fort Mill, South Carolina, United States
      • 205.477.001010 Boehringer Ingelheim Investigational Site
    • Gaffney, South Carolina, United States
      • 205.477.001025 Boehringer Ingelheim Investigational Site
    • Rock Hill, South Carolina, United States
      • 205.477.001002 Boehringer Ingelheim Investigational Site
    • Spartanburg, South Carolina, United States
      • 205.477.001026 Boehringer Ingelheim Investigational Site
    • Union, South Carolina, United States
      • 205.477.001015 Boehringer Ingelheim Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States
      • 205.477.001013 Boehringer Ingelheim Investigational Site
  • Texas
    • Corsicana, Texas, United States
      • 205.477.001022 Boehringer Ingelheim Investigational Site
    • Fort Worth, Texas, United States
      • 205.477.001055 Boehringer Ingelheim Investigational Site
    • Katy, Texas, United States
      • 205.477.001054 Boehringer Ingelheim Investigational Site
    • Tyler, Texas, United States
      • 205.477.001062 Boehringer Ingelheim Investigational Site
  • Virginia
    • Abingdon, Virginia, United States
      • 205.477.001030 Boehringer Ingelheim Investigational Site
    • Roanoke, Virginia, United States
      • 205.477.001008 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Force expiratory volume in 1 second (FEV1)/Force vital capacity (FVC )<0.7(See Section 5.1.2, Pulmonary Function Testing). The diagnosis of COPD can be made at Visit 1 if no Pulmonary Function Testing (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 once a day (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; once a day (QD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug	Change from baseline in trough forced expiratory volume in 1 second (FEV1) 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.	Baseline and 12 weeks
Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	From first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Trough FVC at 12 Weeks on Study Drug	Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.	Baseline and 12 weeks
Percentage of Patients With Adverse Clinical Event on Study	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.	From first drug administration to the last timepoint with information of clinical adverse outcome available, up to 2 years
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)	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.	Baseline and 12 weeks
Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	Baseline and 12 weeks
Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	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 From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Percentage of Patients With 30-day Readmission Rates Outcome Event From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	from date of hospital discharge prior to randomization up to readmission days >1 and <31 days
Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	Start of treatment to the last timepoint with information of clinical adverse outcome available, up to 2 years
Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	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.	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) From the Two Twin Trials, Present 205.477 (NCT01663987) and 205.478 (NCT01662986)	Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported. Time to recovery was assessed with the EXACT-PRO questionnaire. 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. Analysis based on Kaplan Meier estimate.	From first drug administration to the last timepoint with information of EXACT-PRO, up to 2 years

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: August 9, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimate): August 14, 2012

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: September 21, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: 205.477