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

Pulmonary Disease, Chronic Obstructive Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01663987
• Other study ID #: 205.477
• Status: Completed
• Phase: Phase 4
• Start date: August 1, 2012
• Est. completion date: May 1, 2014

Study information

• Verified date: September 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: May 1, 2014
• Est. primary completion date: May 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• tiotropium bromide
18 mcg once a day (QD)
• Placebo
once a day (QD)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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